stripe: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

Gene name - stripe

Synonyms -

Cytological map position - 90E-F

Function - transcription factor

Keyword(s) - ectodermal - muscle attachment

Symbol - sr

FlyBase ID:FBgn0003499

Genetic map position - 3-62.0

Classification - zinc finger

Cellular location - nuclear

NCBI links: Precomputed BLAST | Entrez Gene
Recent literature
Chen, X., Rahman, R., Guo, F. and Rosbash, M. (2016). Genome-wide identification of neuronal activity-regulated genes in Drosophila. Elife 5. PubMed ID: 27936378
Activity-regulated genes (ARGs) are important for neuronal functions like long-term memory and are well-characterized in mammals but poorly studied in other model organisms like Drosophila. This study stimulated fly neurons with different paradigms and identified ARGs using high-throughput sequencing from brains as well as from sorted neurons: they included a narrow set of circadian neurons as well as dopaminergic neurons. Surprisingly, many ARGs are specific to the stimulation paradigm and very specific to neuron type. In addition and unlike mammalian immediate early genes (IEGs), fly ARGs, including hr38, stripe, ring finger protein CG8910, and the protein kinase CG11221, do not have short gene lengths and are less enriched for transcription factor function. Chromatin assays using ATAC-sequencing show that the transcription start sites (TSS) of ARGs do not change with neural firing but are already accessible prior to stimulation. Lastly based on binding site enrichment in ARGs, transcription factor mediators of firing were identified, and neuronal activity reporters were created.

How do muscle cells made in the mesoderm become attached to overlying ectodermal cells in a precise geometric array? Before dealing with the role of stripe in this process, a look at what goes on prior to stripe's involvement is in order.

During germ band shortening, somatic mesodermal cells migrate to their final position in each segment and begin to fuse to founder cells, forming myotubules. Nascent myotubules elongate and migrate toward ectodermal segmental groove cells, the sites of their future attachment. How do these myotubules know where to attach?

The patterning of the epidermis influences the patterning of the mesoderm. It is said that the epidermis provides positional information which controls the oriented migration of myotubes. There is a segmental variation in the expression of twist in the mesoderm that mirrors the segmentation of the ectoderm. High levels of mesodermally located twist are expressed adjacent to ectodermal segmental borders, sites where engrailed is expressed in posterior compartments and wingless (wg) is expressed in adjacent anterior compartments. The level of mesodermal twist sharply declines beneath the epidermal cells expressing engrailed, but gradually expression increases to reach a peak under the cells expressing wg and dpp in the next segment. It is these cells, underneath the cells expressing wg and dpp at the segmental border that are fated to attach to the segmental border. Along with other signals, the chemical signals (DPP and WG) emitted by the segmental border cells and their neighbors communicate information about the site of attachment to the underlying mesodermal cells. (Dunin-Borkowski, 1995).

The stripe gene is involved in the process of epidermal cell recognition of myotubules. stripe is expressed in the epidermis, and mutants exhibit a disruption in myotubule patterning. Stripe is a member of the early growth response family of zinc finger proteins that also includes Krox20, a protein involved in mammalian hindbrain and neural crest development (Lee, 1995).

Another protein expressed in segmental border cells is Groovin. This appears to be the contact protein for myotubules. Groovin immunoreactivity is abolished in both wingless and naked mutant embryos. patched mutants show a duplication in groovin expressing cells and a reduced disruption of muscle pattern. groovin expression is independent of stripe, but apparently their coordinated activity is involved in epidermal interation with mesoderm (Volk, 1994).

Further analysis of Stripe and Groovin reveals the existence of reciprocal signaling between Drosophila epidermal muscle attachment cells and their corresponding muscles. stripe is both necessary and sufficient to initiate the developmental program of epidermal muscle attachment (EMA or segmental border) cells. In stripe mutant embryos, these cells do not differentiate correctly. Ectopic expression of Stripe in various epidermal cells transforms these cells into muscle-attachment cells expressing an array of epidermal muscle attachment cell-specific markers. These markers include goovin, delilah, and beta1 tubulin. The EMA-specific genes induced by Stripe can be divided into two groups: genes that follow Stripe ectopic expression in all embryonic stages or genes that can not be detected in early (stage 10-11) or late (older than stage 14) developmental stages, but only in intervening stages. groovin and alien represent the first group (all stages) and delilah and beta1 tubulin represent the second group (intervening stages) and are expressed only in stages 12-14 (Becker, 1997).

The ectopic epidermal muscle attachment cells are capable of attracting somatic myotubes from a limited distance, providing that the myotube has not yet been attached to or been influenced by a closer wild-type attachment cell. Analysis of the relationships between muscle binding and differentiation of the epidermal muscle attachment cell has been performed in mutant embryos in which either loss-of-muscles or ectopic muscles were induced. This analysis indicates that although the initial expression of epidermal muscle-attachment cell-specific genes including stripe and groovin is muscle independent, continuous gene expression is maintained only in epidermal muscle attachment cells that are connected to muscles. Normally, the expression of beta1 tubulin is restricted to the final stage of gene expression in tendon-like cells, supporting the idea of a distinct mechanism regulating gene expression within the tendon cells as a result of muscle interactions. These results suggest that the binding of a somatic muscle to an epidermal muscle attachment cell triggers a signal affecting gene expression in the attachment cell. Thus there exists a reciprocal signaling mechanism between the approaching muscles and the epidermal muscle attachment cells. First the epidermal muscle attachment cells signal the myotubes and induce myotube attraction and adhesion to their target cells. Following this binding, the muscle cells send a reciprocal signal to the epidermal muscle attachment cells inducing their terminal differentiation into tendon-like cells (Becker, 1997).


cDNA clone length - There are two transcripts, 5.0 and 6.5 kb respectively. The transcripts differ in 5' exons. The 5' end of the SR a transcript is coded for by three exons that differ from the two exons forming the 5' end of the SR b transcript. The two transcipts share three exons coding for the 3' end of both transcripts (Frommer, 1996).


Amino Acids - at least 512

Structural Domains

There are three zinc finger domains in SR. The variable domain in SR, lacking the egr domain of EGR proteins, is a glutamine rich region implicated in transcriptional activation (Lee, 1995).

The Klumpfuss sequence is characterized by four zinc-finger domains of the C2H2 class; part of the N-terminus is negatively charged; the C-terminus, including the zinc-fingers, is positively charged. The N-terminal region contains glutamine-, histidine- and proline-rich stretches, features found in transcriptional activation and repression domains. There are three poly-alanine stretches, two in the N- and one in the C-terminal region. Such stretches are implicated in transcriptional repression. Three putative nuclear localization sites are found in the protein. Klu has a high degree of similarity to the zinc-finger domains of the members of the EGR family. As in WT-1, Klu contains an additional zinc finger (the first) that is only distantly related to those of the EGR proteins. Besides WT-1, Klu is the only other member of the family with four zinc fingers. There is complete conservation of the amino acids that contact the DNA-binding consensus sequence. So far only two other proteins are described as EGR-like in invertebrates, the Drosophila genes stripe and huckebein. Whereas the zinc fingers of Stripe have the characteristic amino acids for the binding of the DNA consensus sequence, in the zinc fingers of Huckebein, four out of the six amino acids are not conserved. However, the overall homology of the Huckebein finger region shows no greater homology to the EGR sequences than does the finger region of Klumpfuss. In comparison, the Stripe sequence shows a much more marked homology to the vertebrate EGR proteins than do the sequences of either Huckebein or Klu (Klein, 1997).

A subset of zinc finger transcription factors, including SR, contain amino acid sequences that resemble those of Krüppel. They are characterized by multiple zinc fingers containing the conserved sequence CX2CX3FX5LX2HX3H (X is any amino acid, and the cysteine and histidine residues are involved in the coordination of zinc) that are separated from each other by a highly conserved 7-amino acid inter-finger spacer, TGEKP(Y/F)X, often referred to as the H/C link.

Each 30-residue zinc finger motif folds to form an independent domain with a single zinc ion tetrahedrally coordinated beween an irregular, antiparallel, two stranded ß-sheet and a short alpha-helix. Each zinc finger of mouse Zif268 (which has three fingers) binds to DNA with the amino terminus of its helix angled down into the major groove. An important contact between the first of the two histidine zinc ligands and the phosphate backbone of the DNA contributes to fixing the orientation of the recognition helix. Although the two fingers of Drosophila Tramtrack interact with DNA in a way very similar to those of Zif268, there are important differences. Tramtrack has an additional amino-terminal ß-strand in the first of the three zinc fingers. The charge-relay zinc-histidine-phosphate contact of Zif268 is substituted by a tyrosine-phosphate contact. In addition, for TTK, the DNA is somewhat distorted with two 20 degree bends. This distortion is correlated with changes from the rather simple periodic pattern of amino base contacts seen in Zif268 and finger 2 of TTK (Klug, 1995 and references).

Zif268-like zinc fingers are generally regarded as independent DNA-binding modules that each specify three base pairs in adjacent, but discrete, subsites. However, crystallographic evidence suggests that a contact also can occur from the second helical position of one finger to the subsite of the preceding finger. For the three-finger DNA-binding domain of the protein Zif268, and a panel of variants, it has been shown that deleting the putative contact from finger 3 can affect the binding specificity for the 5' base in the adjoining triplet, which forms part of the binding site of finger 2. This finding demonstrates that Zif268-like zinc fingers can specify overlapping 4-bp subsites, and that sequence specificity at the boundary between subsites arises from synergy between adjacent fingers. This has important implications for the design and selection of zinc fingers with novel DNA binding specificities (Isalan, 1997).

stripe: Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 10 Sept 97

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