achaete: Biological Overview | Evolutionary Homologs | Transcriptional regulation | Targets of activity | Protein Interactions and Post-transcriptional Regulation | Developmental Biology | Effects of Mutation | References

Gene name - achaete

Synonyms - hairy-wing (HW), T5

Cytological map position - 1B1-2

Function - transcription factor

Keywords - proneural, achaete-scute complex

Symbol - ac

FlyBase ID:FBgn0000022

Genetic map position - 1-0.0

Classification - basic HLH

Cellular location - nuclear



NCBI link: Entrez Gene

achaete orthologs: Biolitmine
Recent literature
Negre, B. and Simpson, P. (2015). The achaete-scute complex in Diptera: patterns of non-coding sequence evolution. J Evol Biol [Epub ahead of print]. PubMed ID: 26134680
Summary:
The achaete-scute complex has been a useful paradigm for the study of pattern formation and its evolution. achaete-scute genes have duplicated and evolved distinct expression patterns during the evolution of cyclorraphous Diptera. Are the expression patterns in different species driven by conserved regulatory elements? If so, when did such regulatory elements arise? Most of the achaete-scute complex of the fly Calliphora vicina (including the genes achaete, scute and lethal of scute) have been sequenced to compare non-coding sequences with known cis-regulatory sequences in Drosophila. The organization of the complex is conserved with respect to Drosophila species. There are numerous small stretches of conserved non-coding sequence that, in spite of high sequence turnover, display binding sites for known transcription factors. Synteny of the blocks of conserved non-coding sequences is maintained suggesting not only conservation of the position of regulatory elements but an origin prior to the divergence between these two species. It is proposed that some of these enhancers originated by duplication with their target genes.
Hsiao, Y. L., Chen, H. W., Chen, K. H., Tan, B. C., Chen, C. H. and Pi, H. (2023). Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation. Development 150(5). PubMed ID: 36897355
Summary:
Neurogenesis is initiated by basic helix-loop-helix proneural proteins. This study showed that Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression. Arp6 mutants exhibit reduced transcription in sensory organ precursors (SOPs) downstream of the proneural protein patterning event. This leads to retarded differentiation and division of SOPs and smaller sensory organs. These phenotypes are also observed in proneural gene hypomorphic mutants. Hypomorphic ac sc mutant recapitulates Arp6 mutant phenotypes. Arp6 also interacted with Sc and Atonal (Ato) but failed to interact with the proneural protein heterodimeric partner Daughterless. Proneural protein expression is not reduced in Arp6 mutants. Enhanced proneural gene expression fails to rescue retarded differentiation in Arp6 mutants, suggesting that Arp6 acts downstream of or in parallel with proneural proteins. H2A.Z mutants display Arp6-like retardation in SOPs. Transcriptomic analyses demonstrate that loss of Arp6 and H2A.Z preferentially decreases expression of proneural protein-activated genes. H2A.Z enrichment in nucleosomes around the transcription start site before neurogenesis correlates highly with greater activation of proneural protein target genes by H2A.Z. It is proposed that upon proneural protein binding to E-box sites, H2A.Z incorporation around the transcription start site allows rapid and efficient activation of target genes, promoting rapid neural differentiation.
BIOLOGICAL OVERVIEW

achaete is a proneural gene of the achaete-scute complex (AS-C). It is expressed in the presumptive neuroectoderm during embryonic development and is responsible for the allocation of specific cells (presumptive neuroblasts) to the neural fate. Neurogenesis is fostered by the interaction of several systems of gene expression. These include lateral inhibition (controlled by the Notch pathway) and proneural gene expression.

The process of allocation differs from the process of directing the specific fate of cells in a differentiation pathway. In the former process, cells are allocated, in effect, set aside and destined for a specific fate. This is the function of the achaete-scute complex. But the latter process brings other genes into play, to direct the specific fate, that is, neural development or Malphigian tubule development or any number of other potential fates.

One particularly intriguing aspect of development is the evolution of species-specific two dimensional patterns. For example, each species of insect has a specific arrangement of bristles and other sensory organs on the adult epidermis. These organs are neural in origin and require the involvement of the AS-C for their proper development. Observations of wing imaginal discs (larval sacs of cells that give rise to adult wings) reveal that achaete and scute are transcribed in a pattern that prefigures the future sites of neural elements.

What aspects of control establish this pattern of as-sc transcription? It is thought that genes that act earlier than the proneural genes establish a prepattern in the wing imaginal disc, and these genes in turn regulate the transcription of ac-sc according to the pattern they set. Candidate genes for this function are found early in development among pair-rule and segment polarity genes that establish the pattern of gene transcription in the embryo. A more proximal cause is the two recently discovered homeodomain proteins, Araucan and Caupolican that are transcribed in a prepattern that prefigures the future site of sensory elements and the wing veins as well (Gomez-Skarmeta, 1996).

An early step in the development of the large mesothoracic bristles (macrochaetae) of Drosophila is the expression of the proneural genes of the achaete-scute complex (AS-C) in small groups of cells (proneural clusters) of the wing imaginal disc. This is followed by a much increased accumulation of AS-C proneural proteins in the cell that will give rise to the sensory organ, the SMC (sensory organ mother cell). This accumulation is driven by cis-regulatory sequences, SMC-specific enhancers, that permit self-stimulation of the achaete, scute and asense proneural genes. Negative interactions among the cells of the cluster, triggered by the proneural proteins and mediated by the Notch receptor (lateral inhibition), block this accumulation in most cluster cells, thereby limiting the number of SMCs. In addition, proneural proteins trigger positive interactions among cells of the cluster that are mediated by the Epidermal growth factor receptor (Egfr) and the Ras/Raf pathway. These interactions, termed 'lateral co-operation', are essential for macrochaetae SMC emergence. Activation of the Efgr/Ras pathway appears to promote proneural gene self-stimulation mediated by the SMC-specific enhancers. Excess Egfr signaling can overrule lateral inhibition and allow adjacent cells to become SMCs and sensory organs. Thus, the Egfr and Notch pathways act antagonistically in notum macrochaetae determination (Culí, 2001).

The earliest stage in macrochaetae development is the formation of the proneural clusters of ac-sc expression. Accumulation of Sc in cells of proneural clusters located at the more central positions of the wing disc decreases upon reduction of the level of Egfr signaling. The effect is cell-autonomous, which indicates that reception of the signal is important for cells to express sc properly. In contrast, more marginally located clusters, like the notopleural or scutellar, are unmodified or slightly enhanced under conditions of insufficient Egfr signaling. It is known that expression of ac-sc in different proneural clusters depends on separate, functionally independent enhancers which are thought to respond to local, specific combinations of transcription factors (prepattern). The different, spatially restricted effects of the insufficiency of Egfr function may thus be due to interference in the deployment or function of particular factors expressed in the affected area. Interestingly, the expression of the homeobox genes of the iroquois complex, necessary for the expression of ac-sc in many notum proneural clusters, is especially sensitive to the expression of the Vein Egfr ligand in the central region of the notum. Alternatively, since Egfr function is a well known requisite for growth and patterning of imaginal discs, the reduced expression of sc may be due to a more general impairment of the patterning of the central area of the disc (Culí, 2001).

The data support a key role for Egfr signaling in the emergence of the notum macrochaetae SMCs from proneural clusters. Indeed, expression of the Egfr inhibitory ligand Aos exclusively in proneural clusters, a condition that permits essentially wild-type Sc accumulation in these clusters, almost completely suppresses the appearance of SMCs and SOs. SMC emergence is also impaired in discs from heat-treated temperature sensitive Egfr larvae and in clones of cells expressing UAS-rafDN2.1. Moreover, when the cells that accumulate RafDN2.1 occupy positions where SMCs normally appear, wild-type neighboring cells give rise to displaced SMCs. This phenomenon is reminiscent of and in accordance with the observation, made with mosaic individuals, that when the position of a dorsocentral bristle is in ac minus territory, this bristle does not develop, but a nearby ac plus cell can give rise to a dorsocentral bristle displaced from its wild-type position. The cell-autonomous effect of RafDN2.1 indicates that reception of the Egfr signal, mediated by the Ras/Raf/MAP kinase cassette, is essential for notum macrochaetae SMC determination. This was further substantiated by the cell autonomous induction of SMCs and bristles in clones of cells overexpressing a constitutively activated form of Ras. Taken together, these results indicate that reception of the Egfr signal promotes sc expression and SMC determination (Culí, 2001).

In the notum anlagen the expression of rho/ve occurs mainly in proneural clusters and this expression is dependent on ac-sc. Rho/ve facilitates the processing of Spitz, an activating ligand of Egfr. The soluble, active form of Spitz promotes ectopic sc expression and SMC emergence. Hence, these data suggest that, in proneural clusters, Ac-Sc promote expression of rho/ve, which by activating Spitz, would stimulate Egfr signaling in the cells of the cluster. (The Vein Egfr ligand probably does not specifically act in proneural clusters, because many of these lie outside of its expression domain). It is thus proposed that Egfr mediates a mutual positive signaling among cells of the proneural cluster, which promotes SMC emergence by probably reinforcing ac-sc expression. This positive signaling is called lateral cooperation. Evidently, this does not exclude an autocrine activation of the Egfr pathway in the cells that express AS-C proteins, but the lateral cooperation hypothesis is favored since it is well established in other systems that the Egfr pathway is used mainly for intercellular communication. This signaling should facilitate the acquisition of the SMC state by one or a few cells of a proneural cluster (Culí, 2001).

The SMC state is associated with greatly increased levels of proneural protein. These are accomplished by the self-stimulation of ac, sc and ase mediated by AS-C enhancers that activate these genes specifically in the cells that become SMCs. Since Ras1V12 elicits the expression of both sc and SRV-lacZ, it is proposed that, in the extant proneural clusters, the SMC-specific enhancers are targets of Egfr signaling. Unidentified effector(s) of the Egfr/Ras pathway should facilitate the self-stimulation of the proneural genes mediated by the SMC-specific enhancers by, possibly, binding to these enhancers. Conclusive evidence in support of this role requires the identification of the signaling effector(s) and of their interaction with the enhancer. Interestingly, overexpression of the effector Pointed P1 promotes development of many extra macrochaetae on the notum and putative Ets-domain binding sites have been identified in the sc and ase SMC enhancers (GTGGAAAT and ACGGAAAC, respectively) (Culí, 2001).

Egfr-mediated lateral cooperation should tend to activate the SMC-specific enhancers in many cells of the proneural clusters. This, however, is prevented by N signaling, which is activated by Ac and Sc in the cells of the cluster. This signaling, by means of the bHLH proteins of the E(spl)-C, blocks the ac-sc-ase self-stimulatory loop promoted by the SMC-specific enhancers. However, within a proneural cluster the cells of the proneural field accumulate greater amounts of Ac-Sc proteins. As it has been hypothesized that cells that signal the most are the least inhibited by their neighbors, eventually, a cell of the proneural field will be released from the inhibitory loop and its levels of E(spl)-C bHLH protein will become minimal. This cell will turn on the ac-sc-ase self-stimulation and become an SMC. The SMC signals maximally to its neighbors and prevents them from following the same fate (lateral inhibition). These results add to this scenario the requirement for Egfr-mediated signaling for one cell of the proneural field to turn on the ac-sc-ase self-stimulatory loops and become an SMC. According to this model, Ac-Sc activate both the N-and Egfr-mediated signaling pathways, with their SMC-suppressing and SMC-promoting abilities, respectively, and both signaling systems appear to act on the same SMC-specific enhancers (Culí, 2001).

AC is not only involved in neurogenesis but also in a number of other morphogenetic events that essentially resemble the actions of AC in neurogenesis. The action of AC in the development of Malphigian tubules is a good example. These excretory organs take the form of four protuberances connected to the proctodeum. Achaete is necessary for cell allocation, but not cell commitment. Achaete function here is identical in manner to its function in neural differentiation. In this case Krüppel directs the differentiation pathway of the allocated cells. Expression of Krüppel is initially weak throughout a broadly diffuse region that with time grows progressively more concentrated, in fewer and fewer cells. Krüppel expression is controlled by forkhead, which in turn is induced by the activity of tailless and huckebein.

By stage 10, Krüppel has become more strongly stained, in still fewer cells (a subset of only 6-8 cells in each primordium), and by stage 12 just the tip cell expresses Krüppel. This single cell is required to direct all cell proliferation in the tubule for which it is a part. Through cell proliferation and migration, lead by the tip cell, the Malpighian tubules elongate until they reach full size. The restriction of Krüppel requires expression of neurogenic genes Delta, Notch and neuralized. In the absence of members of the AS-C, tip cells fail to segregate. Without the activity of the proneural genes, both the mitogenic capacity and the neuronal characteristics of the tip cell are lost. Tip cell allocation would seem to be dependent on the same kinds of genetic interactions required for neurogenesis (Hoch, 1994).

achaete's status as a proneural gene is solidly implanted in the literature. But paradoxically, it is nearly impossible to think of a single gene in the neurogenic pathway that requires achaete for expression, that is, a gene whose promoter binds AC and is activated by that binding. The reason for this dearth of information is the redundancy of the four AS-C genes. Mutations in any one gene produces little phenotypic effect. A good indication of genes regulated by Achaete can be found at the daughterless site. Mutations in daughterless, which codes for Achaete's dimerization partner, eliminate expression of AC target genes.

AC does bind to the promoter of Enhancer of split complex genes and activates their transcription. Since E(spl)-C genes inhibit neurogenesis such binding presents yet another paradox. It should be remembered that achaete is expressed in cells that by default will remain in the epidermal cell layer, inhibited from adopting the neural fate. Thus achaete has well defined neurogenic (anti-neural) effects.

The neurogenic effects of achaete can be contrasted with its proneural effects, representing the primary function of achaete. achaete expression is enhanced in cells which will delaminate from the neuroectoderm and become neuroblasts. What genes are regulated by this enhanced expression of achaete? It is probably true that achaete is only required transiently, that is, it is required to stimulate the proneural fate by allocating cells to that fate but is not required to carry out the development of that fate. It remains for future achaete research to unravel what its positive effects are on neurogenesis, and for that matter, on the other developmental pathways in which it is involved.

Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator

The zinc-finger transcription factor Senseless is co-expressed with basic helix-loop-helix (bHLH) proneural proteins in Drosophila sensory organ precursors and is required for their normal development. High levels of Senseless synergize with bHLH proteins and upregulate target gene expression, whereas low levels of Senseless act as a repressor in vivo. However, the molecular mechanism for this dual role is unknown. This study shows that Senseless binds bHLH proneural proteins, including Achaete, Scute, and Daughterless, via its core zinc fingers and is recruited by proneural proteins to their target enhancers to function as a co-activator. Some point mutations in the Senseless zinc-finger region abolish its DNA-binding ability but partially spare the ability of Senseless to synergize with proneural proteins and to induce sensory organ formation in vivo. Therefore, it is proposed that the structural basis for the switch between the repressor and co-activator functions of Senseless is the ability of its core zinc fingers to interact physically with both DNA and bHLH proneural proteins. Since Senseless zinc fingers are ~90% identical to the corresponding zinc fingers of its vertebrate homologue Gfi1, which is thought to cooperate with bHLH proteins in several contexts, the Senseless/bHLH interaction might be evolutionarily conserved (Acar, 2006).

The Sens protein has been shown to act as a transcriptional repressor and activator, depending on its relative abundance in relation to proneural proteins. The reporter construct used in that study consists of the ac proximal enhancer/promoter region upstream of the firefly luciferase coding sequence. This ac enhancer contains a Sens-binding site (S-box: AATC) and three E-boxes, known binding sites for proneural proteins. Proneural proteins heterodimerize with Daughterless (Da) via their bHLH domains and bind to the E-boxes on ac-luc to upregulate transcription. Depending on the amount of ac and da expression constructs transfected, the luciferase expression from this reporter can be increased 10 to 1000 times the basal level. To obtain the optimal sensitivity in the transcription assays, low levels of proneural expression constructs (1-2 ng) were used to assess the transcriptional activation potential of Sens (activation assay), and higher levels of proneurals (10 ng) to assess the transcriptional repression potential of Sens (repression assay). In the absence of Ac and Da, Sens does not activate or repress ac transcription (Acar, 2006).

Based on evolutionary conservation with its vertebrate homologues, Sens can be divided into two domains: an N-terminal domain of 414 amino acids, which shows little homology with other GPS proteins, and a C terminal domain of 127 amino acids, which exhibits strong homology with other GPS proteins and contains four highly conserved C2H2-type Zn fingers. Sens was aligned to its closest homologue from the mosquito Anopheles gambiae, which is thought to have diverged from Drosophila about 180 million years ago, and nine conserved stretches of 6-10 amino acids were found in the Sens N-terminal domain. Mutational analysis of the conserved stretches followed by transcription assays indicate that the individual conserved motifs in the N-terminal domain are not important for the activation and repression mediated on ac by Sens (Acar, 2006).

Four C2H2-type Zn-finger domains of the GPS proteins mediate DNA binding. Deletion analysis of Gfi1 Zn fingers has shown that Zn fingers 3-5 of Gfi1, which correspond to Zn fingers 1-3 of Sens, are required for DNA binding. To begin to assess the precise role of individual Zn fingers in the repressor and activator functions of Sens, each Zn finger in Sens was mutated and the ability of the mutant Sens proteins to bind DNA in electromobility shift assays (EMSA) was assayed. Two types of mutants were generated for each Zn finger. In the first group (Sens-1CC, Sens-2CC, Sens-3CC and Sens-4CC), the two cysteines in the C2H2 structure were mutated to alanines. These mutations probably disrupt the structure of the individual Zn fingers. In the second group (Sens-1RTT, Sens-2QDK, Sens-3QNT and Sens-4RDR), the amino acids were altered that have been predicted to directly contact DNA to alanines. Since these amino acids are not crucial for the Zn-finger structure these mutations should abolish direct contact with specific DNA targets but at least partially preserve the overall Zn-finger structure (Acar, 2006).

To determine protein-DNA interactions and relative binding affinities of the mutant Sens proteins for DNA, two different probes were used in EMSA assays. To detect weak protein-DNA interactions, a previously characterized Gfi1-binding site called R21, to which the wild-type Sens is able to bind strongly, was used as a probe. Sens-1CC, Sens-2CC and Sens-3CC proteins lose their ability to bind the R21 probe, suggesting that Zn fingers 1, 2 and 3 are required for DNA binding. However, in agreement with Gfi1 data, Sens-4CC can bind DNA, suggesting that Zn finger 4 is not essential for DNA binding. The second group of Sens Zn-finger mutants behave somewhat differently in the EMSA. Sens-2QDK, Sens-3QNT and Sens-4RDR behave similarly to their CC counterparts, indicating that the amino acids predicted to directly contact the R21 probe in Zn fingers 2 and 3 are crucially important for DNA binding. However, unlike Sens-1CC, Sens-1RTT is still able to bind the R21 probe, albeit weaker than wild-type Sens and Zn-finger 4 mutants. This difference suggests that although Zn finger 1 is required for DNA binding, its role in DNA binding is more complex than a direct contact between the RTT amino acids and DNA (Acar, 2006).

The S-box in the ac promoter was used as a probe in the EMSA assay to determine the binding affinities of mutant Sens proteins for the endogenous Sens-binding site. Wild-type Sens and Sens-4CC but not Sens-1CC, Sens-2CC nor Sens-3CC are able to bind to the S-box probe. Moreover, in line with the R21 data, the Sens-1RTT binds much weaker than wild-type Sens and Sens-4CC. Note that the Sens-4CC binding affinity for the S-box is weaker than wild-type Sens, suggesting that although Zn finger 4 is not essential for DNA binding, it may increase the strength of Sens-DNA interaction (Acar, 2006).

To determine the importance of each Zn-finger domain for the activation and repression mediated by Sens, the mutants were tested in the S2 cell transcription assay. In the activation assay (ac-da, 2ng), wild-type Sens can synergize with Ac-Da and increase the transcription induced by Ac-Da about 18 times. Sens-2CC and Sens-3CC failed to synergize with Ac-Da. Sens-4CC and especially Sens-1CC exhibited significantly less synergism than wild-type Sens. Similar results were obtained for Sens-1RTT, Sens2-QDK, Sens-3QNT and Sens-4RDR. These data indicate that all Zn fingers cooperate in the Sens/bHLH synergism. However, Zn fingers 2 and 3 are indispensable for this process (Acar, 2006).

To test the ability of the Zn-finger mutants to repress ac transcription, the 'repression assay' was used. Low levels of wild-type Sens repress transcription in this assay and as the Sens to proneural ratio increases, the Sens activity switches from a repressor to an activator. Sens-4CC and Sens-4RDR behave essentially as wild-type proteins in this assay. By contrast, mutations in Zn fingers 1, 2 or 3 abolish the repression function of Sens, corroborating the correlation between Sens DNA binding and repression. Interestingly, Sens-1CC and Sens-1RTT display transcriptional activation at a lower Sens to proneural ratio compared with the wild-type Sens, providing further evidence for the negative contribution of Sens DNA-binding to its ability to synergize with proneural proteins. Similar to the data obtained from the 'activation assay.' Sens proteins with mutations in Zn finger 2 or 3 do not show any premature synergism with Ac-Da, highlighting the role of these core Zn fingers in both synergism and repression. Together, these data indicate specific roles for the Zn fingers in repression and activation (Acar, 2006).

Based on the current data, the following model is proposed for the role of Sens in transcriptional regulation of proneural target genes in sensory precursors. Early in the proneural cluster, proneural gene expression is under the control of proneural and E(spl) proteins. At this stage, proneural genes start to engage in a positive autoregulatory loop by binding to the E-boxes in their own enhancers. Initially, low levels of Sens bind DNA rather than the proneural proteins via its Zn fingers because it has a higher affinity for DNA. When bound to DNA, Sens acts as a repressor. Since Sens interacts with several E(spl) proteins, recruitment of E(spl) through Sens might contribute to the negative regulation of proneural target enhancer. As the level of proneural proteins increases, proneural proteins induce more Sens expression. This will lead to saturation of the S-boxes. Additional Sens will bind proneural proteins via its core Zn-finger domains and act as a co-activator to increase the transcription induced by proneural proteins. It is proposed that the switch between the repressor and co-activator functions of Sens depends on the conformational state of its Zn fingers. In this model, binding to proneural proteins will allow the Sens Zn fingers to adopt an alternative conformation compared to the DNA-bound state. This will enable Sens to cooperate with co-activators already recruited by proneural proteins, or to recruit new co-activators to further increase the ability of proneural proteins to increase the expression of their target genes in some contexts. This conformation-based hypothesis is supported by the observation that even point mutations in Sens Zn fingers that are dispensable for proneural interaction still cause severe reduction in the synergism between Sens and proneural proteins (Acar, 2006).

Multiple lines of evidence suggest that Sens acts as a transcriptional co-activator for bHLH proneural proteins. First, Sens is required for the upregulation and maintenance of proneural gene expression in the wing margin chemosensory SOPs. Second, Sens synergizes with proneural proteins to upregulate the expression of the ac proximal enhancer in S2 cell assays. Third, ectopic expression of Sens induces ectopic proneural gene expression. Fourth, Sens physically binds bHLH proteins via the core region of its Zn-finger domain. Fifth, Sens can not induce transcription in the absence of proneural proteins. It should be mentioned that in vitro and in vivo observations indicate that DNA binding is not essential for the ability of Sens to act as a co-activator and to induce SOP formation. Therefore, since SOPs accumulate high levels of both proneural proteins and Sens, it is likely that proneural target enhancers that do not contain a Sens-binding site might also be a target for proneural-Sens transcriptional synergism (Acar, 2006).

Similar to its vertebrate homologues, Sens can function as a transcriptional repressor when bound to DNA. Mutational analysis of Sens Zn fingers also indicates a link between DNA binding and the repressor function of Sens: those Sens mutants that do not bind DNA (1CC, 2CC and 3CC) fail to repress ac transcription, whereas mutating Zn finger 4, which does not play a major role in DNA binding, does not affect the repressor function of Sens. Although the repressor function seems to be less crucial than the co-activator function in vivo, these data suggest that the repressor function of Sens also contributes to its role in PNS development (Acar, 2006).

Sens physically interacts with proneural proteins via its Zn-finger domains, which are highly conserved between Sens and its vertebrate homologues. In addition, Sens can synergize with the mouse Ato homologue Math1 (Atoh1- Mouse Genome Informatics), when the two proteins are co-expressed in flies. Together, these observations suggest that the Sens-bHLH interaction is evolutionarily conserved. In other words, vertebrate bHLH proteins such as Math1, Mash1 (AScl1- Mouse Genome Informatics) and Math5 (Atoh7- Mouse Genome Informatics), which are co-expressed with Gfi1 in mouse tissues, might be able to recruit Gfi1 to their target enhancers (Acar, 2006).

In conclusion, the data suggest that Sens, a C2H2-type Zn-finger protein, binds to bHLH proneural proteins via its core Zn-finger domains and acts as a co-activator of the expression induced by proneural proteins. Sens can bind to various bHLH proteins and synergize with fly proteins, as well as some of their vertebrate homologues in vivo. These data, together with other examples of Zn-finger/bHLH synergism, suggest that physical and genetic interactions of this type might be a common mechanism for Zn-finger/bHLH cooperation during development (Acar, 2006).


GENE STRUCTURE

cDNA clone length - 912

Bases in 5' UTR - 63

Exons - one

Bases in 3' UTR - 246; there are three polyadenylation signals


PROTEIN STRUCTURE

Amino Acids - 201

Structural Domains

Achaete has a central bHLH domain and a C-terminal acidic domain (Villares, 1987).


achaete: Evolutionary Homologs | Transcriptional regulation | Targets of activity | Protein Interactions and Post-transcriptional Regulation | Developmental Biology | Effects of Mutation | References
date revised: 2 June 2001 

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