osa/eyelid
The distribution of Eld is ubiquitous in early embryos, showing no hint of a striped pattern. It is also ubiquitious in wing discs. Although the protein is present everywhere in eye discs, its strongest expression occurs in a band just anterior to the morphogenetic furrow, in the postion where cells respond to Hedgehog and Decapentaplegic signaling (Treisman, 1997).
Very few eyelid mutant cells are found when clones mutant for eld are analyzed in adult eyes. However, such clones are associated with scars, suggesting that eld mutant cells are present at a certain stage but interfer with normal develpment. The eld mutant clones are relatively small compared with clones mutant for other genes, suggesting that eld is required for cell proliferation and/or survival. Exceptions are clones that include the posterior margin of the disc, which were frequently much larger than internal clones. The difference might lie in the fact that development at the posterior margin is driven by dpp whereas the internal propagation of the furrow depends on hedgehog (Treisman, 1997).
eld also has an affect on neuronal differentiation. Most photoreceptor clusters that form within eld clones contain fewer neuronal cells than normal; therefore, there may be a partial, though not absolute, requirement for eld for neuronal differentiation. The lack of differentiation is not simply attributable to poor cell viability, as all the cells in eld clones can be induced to differentiate as neurons by removing the function of Enhancer of split complex genes. The block to differentiation caused by loss of eld function in the eye resembles the effect of loss of shaggy or ectopic expression of wingless (Treisman, 1997).
Clones of eld mutant cells induced in the wing disc also produce pattern alterations suggestive of antagonism to wingless. One effect of clones produced early in development is the transformation of the posterior notum into a partial second wing. These wings have a reversed anterior-posterior polarity; their most clearly differentiated structure is an alula produced consistently at their anterior margin. This transformation is the reverse of that produced by the wingless1 mutation, which transforms the wing into a duplicated notum, and is similar to that produced by overexpressing wingless, decapentaplegic or optomotor-blind in the notum. Clones induced later in wing development are associated with ectopic wing margin bristles. Many or all of these ectopic bristles are not mutant for eld but they are sometimes seen to form adjacent to eld clones. Ectopic bristle formation is restricted to the dorsal surface of the wing within the anterior compartment, and is observed most commonly near the wing margin in tufts of the bristle type appropriate to their postion along the anterior-posterior axis. Ectopic wing margin bristles are also produced in clones mutant for shaggy. However, shaggy clones show neither the non-autonomy nor the positional restrictions observed for eld clones. These results suggest a cell non-autonomous role for eld in wing patterning (Treisman, 1997).
The activity of the E2F transcription factor is regulated in part by pRB, the
protein product of the retinoblastoma tumor suppressor gene. Studies of tumor
cells show that the p16ink4a/cdk4/cyclin D/pRB pathway is mutated in
most forms of cancer, suggesting that the deregulation of E2F, and hence the cell
cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or
suppress E2F activity are likely to alter cell-cycle control and may play a role
in tumorigenesis. An E2F overexpression phenotype in the Drosophila eye was use
to screen for modifiers of E2F activity. Coexpression of dE2F and its
heterodimeric partner dDP in the fly eye induces S phases and cell death. Thirty
three enhancer mutations of this phenotype were isolated by EMS and X-ray
mutagenesis and by screening a deficiency library collection. The majority of
these mutations sorted into six complementation groups, five of which have been
identified as alleles of brahma (brm), moira (mor),
osa, pointed (pnt), and polycephalon (poc).
osa, brm, and mor encode proteins with homology to SWI1, SWI2, and
SWI3, respectively, suggesting that the activity of a SWI/SNF
chromatin-remodeling complex has an important impact on E2F-dependent phenotypes.
Mutations in poc also suppress phenotypes caused by p21CIP1
expression, indicating an important role for Polycephalon in cell-cycle control
(Staehling-Hampton, 1999).
The molecular basis of the interaction between E2F and a BRM/MOR/OSA
chromatin-remodeling complex is not yet clear and a range of possibilities exists.
The genetic interaction may result from a direct physical interaction between
RBF/E2F complexes and chromatin-remodeling machinery. In support of this idea the
human homologs of BRM, hBRM, and BRG1 have been found to physically associate
with pRB. This raises the possibility that
BRM/MOR/OSA may help E2F/RBF repressor complexes bind to their target sites. This
interpretation is supported by experiments from Trouche and co-workers who used
transient transfection of mammalian cells to demonstrate that BRG1 can cooperate
with pRB to repress E2F-dependent transcription (Trouche, 1997). Consistent with this model,
the
introduction of two copies of GMR-RBF into a GMR-dE2FdDPp35/+;
brm-/+ background suppresses the enhancement by brm. Thus
the effect caused by low levels of brm can be overcome by increasing the
dosage of RBF. Additional evidence has been sought that
would be predicted by this model; to date, however, these experiments have been
inconclusive. BRM lacks the LXCXE motifs found in hBRM and BRG1, which have been
suggested to mediate the interaction with pRB. To date no physical interaction between BRM and RBF
or between BRM and dE2F has been detected. The interaction between endogenous pRB and hBRM or BRG1
proteins is hard to detect even in mammalian cells, and the failure to find
BRM/RBF complexes may simply reflect difficulty in extracting
chromatin-associated proteins under conditions that maintain the interaction (Staehling-Hampton, 1999).
An alternative possibility is that the BRM/MOR/OSA chromatin-remodeling
complex is an important regulator of the expression of some key E2F-target genes,
but this complex does not interact directly with either RBF or E2F. In this case
the functional interaction occurs because these proteins converge on overlapping
sets of promoters. This model is difficult to test because it is not yet clear
which, and how many, E2F target genes are functionally significant. RNR2,
one example of an E2F-dependent gene, is expressed normally in embryos mutant for
brm, osa, or mor; no
change in the expression of RNR2 in GMR-dE2FdDPp35 eye disks
heterozygous for brm, osa, or mor alleles could be detected. While RNR2
expression is often used to provide an in vivo readout of E2F activity,
experiments suggest that it is not a critical E2F target. The effects of brm, mor,
and osa may only be evident at a subset of E2F-regulated promoters and an
extensive screen of E2F targets will be necessary to find the appropriate gene (Staehling-Hampton, 1999).
It is possible that E2F and brm act in distinct pathways that
influence cell-cycle progression. In this model the activity of a
BRM/MOR/OSA-containing complex may have a function that influences the ability of
E2F or RBF to control S-phase entry. Several observations have linked BRM-related
proteins to cell-cycle control. brm null clones in the adult cuticle often
show duplications of bristle structures, suggesting a possible role for
brm in proliferation, and mice lacking the BRM homolog
SNF2alpha show evidence of increased cell
proliferation. Although brm, mor, and
osa have no effect on the GMR-p21 phenotype, both
brm and mor mutations have been isolated as suppressors of a
hypomorphic cyclin E eye phenotype, demonstrating that brm and
mor can affect other cell-cycle phenotypes in the eye. Other studies have shown that
the activity of hSWI/SNF complexes is itself cell-cycle regulated. Transformation by activated Ras
decreases the expression of the murine ortholog of hBRM in mouse fibroblasts, whereas growth
arrest leads to an accumulation of protein. Recently, BRG1 and BAF155, a human
ortholog of Moira, have been shown to associate with cyclin E and are suggested to be
targets for cyclin E-dependent kinases during S-phase entry (Staehling-Hampton, 1999 and references).
During this study it was observed that GMR-dE2FdDP p35/+;
brm-/+ eyes develop necrotic patches that increase in severity
with the age of the adult fly. This raised the possibility that brm
mutations might enhance the phenotype by promoting E2F-induced apoptosis.
However, further experiments have failed to support this hypothesis. brm
mutations fail to enhance the GMR-dE2FdDP phenotype, which has elevated
levels of apoptosis, or to modify a GMR-rpr phenotype. In addition,
brm mutations have no effect on the phenotype of animals in which
GMR-rpr and GMR-hid-induced apoptosis is blocked by GMR-p35.
No increase in the number of apoptotic cells is detected when
GMR-dE2FdDPp35/+; brm-/+ third instar eye disks are
stained with acridine orange (Staehling-Hampton, 1999).
The promoters of Drosophila genes encoding DNA
replication-related proteins contain transcription
regulatory element DRE (5'-TATCGATA) in addition to
E2F recognition sites. A specific DRE-binding factor, DNA replication-related element factor or DREF, positively regulates DRE-containing genes. In addition, it has been
reported that DREF can bind to a sequence in the hsp70 scs'
chromatin boundary element that is also recognized by boundary element-associated factor, and thus DREF may participate in regulating insulator activity. To examine DREF function in vivo, transgenic flies were
established in which ectopic expression of DREF was
targeted to the eye imaginal discs. Adult flies expressing DREF
exhibited a severe rough eye phenotype. Expression of DREF induces
ectopic DNA synthesis in the cells behind the morphogenetic
furrow that are normally postmitotic, and abolishes
photoreceptor specifications of R1, R6, and R7.
Furthermore, DREF expression caused apoptosis in the imaginal
disc cells in the region where commitment to R1/R6 cells takes place,
suggesting that failure of differentiation of R1/R6 photoreceptor cells
might cause apoptosis. The DREF-induced rough eye phenotype is
suppressed by a half-dose reduction of the E2F gene, one of
the genes regulated by DREF, indicating that the DREF
overexpression phenotype is useful to screen for modifiers of DREF
activity. Among Polycomb/trithorax group genes, it was found that a half-dose reduction of some of the trithorax group
genes involved in determining chromatin structure or chromatin
remodeling (brahma, moira, and osa)
significantly suppresses and that reduction of Distal-less
enhances the DREF-induced rough eye phenotype. The results suggest a
possibility that DREF activity might be regulated by protein
complexes that play a role in modulating chromatin structure. Genetic
crosses of transgenic flies expressing DREF to a collection of
Drosophila deficiency stocks allowed identification of several
genomic regions, deletions of which caused enhancement or suppression
of the DREF-induced rough eye phenotype. These deletions should be useful to identify novel targets of DREF and its positive or negative regulators (Hirose, 2001).
The GATA factor Pannier activates proneural achaete/scute (ac/sc) expression
during development of the sensory organs of Drosophila through enhancer binding.
Chip bridges Pannier with the (Ac/Sc)-Daughterless heterodimers bound to the
promoter and facilitates the enhancer-promoter communication required for
proneural development. This communication is regulated by Osa,
which is recruited by Pannier and Chip. Osa belongs to Brahma chromatin
remodeling complexes, and this study shows that Osa negatively regulates ac/sc.
Consequently, Pannier and Chip also play an essential role during repression of
proneural gene expression. This study suggests that altering chromatin structure
is essential for regulation of enhancer-promoter communication (Heitzler, 2003).
ChipE is a viable allele of Chip that
is associated with a point mutation in the LIM-interacting domain
(LID), which specifically reduces interaction with the bHLH proteins
Ac, Sc, and Da. As a consequence, the ChipE mutation
disrupts the functioning of the proneural complex encompassing Chip,
Pnr, Ac/Sc, and Da. A homozygous ChipE mutant
shows thoracic cleft and loss of the DC
bristles, similar to loss of function pnr alleles (Heitzler, 2003).
To identify new factors that regulate this proneural complex, a
screen was performed for second-site modifiers of the ChipE
phenotypes. One allele
of osa (osaE17) was found among the putative mutants.
OsaE17 corresponds to a loss-of-function allele, and
homozygous embryos die with normal cuticle patterning. Both
osaE17 and null alleles of osa
(osa616 or osa14060) enhance the
cleft but suppress the loss of DC bristle phenotypes of
ChipE flies. Indeed, ChipE flies
with only one copy of osa+
(ChipE;osa616/+) are weak and sterile
but show wild-type DC bristle pattern (Heitzler, 2003).
These genetic interactions suggest that Osa can antagonize the function
of Pnr. Moreover, overexpressed Osa
(+/UAS-osa;Gal4-pnrMD237/+) induces a thoracic cleft
and the loss of DC bristles
similar to the loss-of-function pnr alleles. In contrast, loss-of-function
osa alleles display an excess of DC bristles similar to
overexpressed Pnr. For example,
(osa14060/+), (osa616/+), and
(osaE17/+) flies exhibit respectively
2.35 ± 0.12, 2.38 ± 0.12, and 2.43 ± 0.17 DC bristles per
heminotum (Oregon wild-type flies have 2.00 DC bristles/heminotum).
Furthermore, transallelic combination of osa14060
with the hypomorphic osa4H
(osa4H/osa14060) accentuates the excess of
DC bristles compared with (osa14060/+).
(osa4H/osa14060) flies display
4.17 ± 0.19 DC bristles per heminotum. In contrast,
(osa4H/osa4H) flies display 2.50 ± 0.11
DC bristles per hemithorax. The development of the extra DC bristles
revealed by phenotypic analysis was compared with the positions of the
DC bristle precursors detected with a LacZ insert, A101, in
the neuralized gene that exhibits
staining in all sensory organs. In
(osa14060/osa4H) discs, additional DC
precursors are observed that lead to the excess of DC bristles.
The pnrD alleles encode Pnr proteins carrying a
single amino acid substitution in the DNA binding domain that disrupts
interaction with the U-shaped (Ush) antagonist.
Consequently, PnrD constitutively
activates ac/sc, leading to an excess of DC bristles.
This excess is accentuated when osa function is simultaneously reduced (pnrD1/osa616) (Heitzler, 2003).
Since osa shows genetic interactions with trithorax
group genes encoding components of the Brm complex like moira
(mor) and brm, whether mutations in
mor and brm suppress the ChipE
phenotype was investigated. Loss of one copy of brm+ in
(ChipE; brm2/+) flies suppresses the lack
of DC bristles observed in ChipE flies,
similar to loss of one copy of osa+. This
shows that brm and osa both act during Pnr-dependent patterning, in agreement with the fact that they have been shown to be
associated in the Brm complex. In contrast, reducing the amount of Mor
by half [(ChipE;mor1/+) flies] is not
sufficient to modify the ChipE phenotype. This does not definitely exclude the possibility that
mor is directly or indirectly involved, via the Brm complex,
in Pnr-dependent patterning (Heitzler, 2003).
The complete osa open reading frame of 2715 amino acids and
the intronic splicing signals were PCR amplified from genomic DNA
prepared from homozygous embryos (osaE17 and
osa14060) and homozygous first instar larvae
(osa4H). For osa14060 and
osa4H, the sequence analysis revealed a single
mutation in the N terminus that causes a glutamine to stop codon
substitution. The conceptual translation of
osa14060 leads to a truncated Osa protein lacking both
functional domains, whereas Osa4H retains the ARID domain but
lacks the C-terminal EHD. Wild-type osa function is
necessary for patterning of the DC bristles. Although
osaE17 behaves as a stronger allele than
osa14060 and osa4H, molecular identity of the mutation is unknown.
Hence, the osaE17 phenotype may result from a mutation in
regulatory sequences that affects osa expression (Heitzler, 2003).
It has been shown that a complex containing Pnr, Chip, and the
(Ac/Sc)-Da heterodimer activates proneural expression in the DC
proneural cluster and promotes development of the DC macrochaetae.
Osa and Pnr/Chip have antagonistic activities
during development because loss of osa function
(osa4H and osa14060) displays
additional DC bristles. However, since the current study reveals that
osa genetically interacts with pnr and Chip,
it was asked whether Osa physically interacts with the Pnr and Chip
proteins. Immunoprecipitations of protein extracts made
from Cos cells cotransfected with expression vectors for tagged Osa and
either Pnr or tagged Chip were immunoprecipitated.
Because Osa is a large protein, several expression vectors
encoding contiguous domains of Osa were used. Osa
coimmunoprecipitates with Pnr and Chip and can be detected
on Western blots with appropriate antibodies. The interactions appear
to require the overlapping domains Osa E (His1733/Glu2550) and Osa F
(Ala2339/Ala2715) corresponding to the EHD.
Enhancer-promoter communication during proneural activation and
development of the DC bristles requires regulatory sequences scattered
over large distances and appears to be negatively regulated by
interaction of Pnr and Chip with Osa through the EHD. Interestingly,
the EHD is not conserved in yeast. In yeast, the UAS sequences are
generally close to the promoter and there is no requirement for
long-distance interactions. This observation could support the idea
that the EHD is essential for long-distance enhancer-promoter
communication. Alternatively, yeast may just lack proteins like Chip or Pnr (Heitzler, 2003).
The DNA-binding domain and the C-terminal region are essential for the
function of Pnr during development of the DC sensory organs. The pnrVX1 and pnrVX4
alleles (collectively pnrVX1/4) are characterized by
frameshift deletions that remove two C-terminal alpha-helices and result
in reduced proneural expression and loss of DC bristles (Heitzler, 2003).
The molecular interactions between Osa and
PnrD1 and between Osa and PnrVX1 were investigated.
PnrD1 protein interacts with the EHD as efficiently as
wild-type Pnr. In
contrast, the physical interaction is disrupted when the C terminus of
Pnr encompassing the alpha-helices is removed.
Because the C terminus of Pnr is required for the Pnr-Osa interaction
in transfected cells extracts, the abilities of in vitro
translated 35S-labeled Osa domains to bind to GST-CTPnr
attached to glutathione-bearing beads were investigated.
Only Osa E and Osa F interact with the C terminus of Pnr. The
interaction between Chip and Osa, and it was found that Osa associates with
the N-terminal homodimerization domain of Chip,
also required for the interaction between Chip and Pnr, was investigated. Furthermore,
Osa E and Osa F also bind to immobilized GST-Chip.
Deletion of the alpha helix H1 disrupts the interactions
between Pnr and Osa. Interestingly, the same deletion
also disrupts the interaction with Chip.
Therefore, the functional antagonism between Chip and Osa during neural
development may result from a competition between these proteins for
association with Pnr. Alternatively, the deletion of H1 may affect the
overall structure of the C terminus of Pnr and disrupt the physical
interactions with Chip and Osa. To discriminate between these
hypotheses, immunoprecipitations of protein extracts
containing a constant amount of Pnr, a constant amount of the tagged
Osa E domain, and increasing concentrations of Chip were performed.
Pnr immunoprecipitates with
immunoprecipitated tagged Osa E and the amount of Pnr
immunoprecipitated increases in the presence of increasing
concentrations of Chip. The presence of increasing amounts of Chip does
not inhibit the Osa-Pnr interaction as would be expected if Osa and
Chip were to compete for binding to Pnr. In contrast, it suggests that
Chip and Pnr act together to recruit Osa and to target its activity and
possibly the activity of the Brm complex to the ac/sc promoter
sequences (Heitzler, 2003).
Using expression vectors encoding contiguous domains of Osa, it was shown
that the EHD of Osa mediates interactions with Pnr and Chip. Because
the EHD is lacking in the truncated Osa14060 and
Osa4H, it is hypothesized that the loss of interaction with Pnr
and Chip are responsible for the excess of DC bristles observed in
osa4H and osa14060 (Heitzler, 2003).
To investigate whether these interactions between Osa, Pnr, and Chip
function in vivo during DC bristle development, the
effects of both loss of function and overexpression of osa were examined on
the activity of a LacZ reporter whose expression is driven by
a minimal promoter sequence of ac fused to the DC enhancer (transgenic line DC:ac-LacZ).
It was found that expression of the LacZ transgene is
increased in osa14060/osa4H wing discs
when compared with the wild-type control. For
overexpression experiments, the UAS/GAL4 system was used, using as a driver the pnrMD237 strain
that carries a GAL4-containing transposon inserted in the pnr
locus (driver: pnr-Gal4). This insert gives an expression pattern of
Gal4 indistinguishable from that of pnr. It was found that overexpressed Osa
leads to a
strong reduction of LacZ staining in the DC area, consistent with
the lack of DC bristles. Thus, overexpressed Osa represses activity of the
ac promoter sequences required for DC ac/sc
expression and development of the DC bristles. It has been previously
reported that wingless expression is also required for
patterning of the DC bristles. However, the
repressing effect of Osa on development of the DC bristles is unlikely
to be the result of an effect of Osa on wingless expression
because overexpressed Osa driven by pnrMD237 has no
effect on the expression of a LacZ reporter inserted into the
wingless locus. Thus, Osa acts through the DC enhancer of the
ac/sc promoter sequences to repress ac/sc and neural
development (Heitzler, 2003).
ChipE disrupts the enhancer-promoter communication
and strongly affects expression of the LacZ reporter driven by
the ac promoter linked to the DC enhancer.
Because null alleles of osa suppress the loss of
DC bristles displayed by ChipE, the
consequences of reducing the dosage of osa was examined in
ChipE flies. The expression of the
LacZ reporter is not affected in ChipE
flies when Osa concentration is simultaneously reduced (Heitzler, 2003).
In conclusion, Pnr function during
proneural patterning is regulated by interaction with several transcription factors.
Pnr function is negatively regulated by Ush, which interacts with its DNA-binding domain.
Chip associates with the C terminus of Pnr, bridging Pnr at the
DC enhancer with the AC/Sc-Da heterodimers bound at the proneural
promoters, thus activating proneural gene expression.
The current study reveals that Pnr function can also be
regulated by interaction with Osa. Thus, Osa activity is specifically
targeted to ac/sc promoter sequences and the binding of Osa
therefore has a negative effect on Pnr function, leading to reduced
expression of the proneural ac/sc genes. Osa belongs to Brm
complexes, which are believed to play an essential role during
chromatin remodeling necessary for gene expression. For example, in
vitro transcription experiments with nucleosome assembled human
beta-globin promoters have shown that the BRG1 and BAF155 subunits of
the mammalian SWI/SNF homolog are essential to target chromatin remodeling and promote
transcription initiation mediated by GATA-1. In contrast to what was observed in vitro, the current
results suggest that in vivo the SWI/SNF complexes can also act to
remodel chromatin in a way that represses transcription. Alternatively,
the observed repression of proneural genes may simply define a novel
function of Osa, independent of chromatin remodeling (Heitzler, 2003).
The establishment of the dorsal-ventral axis of the Drosophila wing depends on
the activity of the LIM-homeodomain protein Apterous. Apterous activity depends
on the formation of a higher order complex with its cofactor Chip to induce the
expression of its target genes. Apterous activity levels are modulated during
development by dLMO (Beadex). Expression of dLMO in the Drosophila wing is regulated by
two distinct Chip dependent mechanisms. Early in development, Chip bridges two
molecules of Apterous to induce expression of dLMO in the dorsal compartment.
Later in development, Chip, independently of Apterous, is required for
expression of dLMO in the wing pouch. A modular P-element
based EP (enhancer/promoter) misexpression screen was conducted to look for genes involved in
Apterous activity. Osa, a member of the Brahma
chromatin-remodeling complex, was found to be a positive modulator of Apterous activity in
the Drosophila wing. Osa mediates activation of some Apterous target genes and
repression of others, including dLMO. Osa has been shown to bind Chip. It is
proposed that Chip recruits Osa to the Apterous target genes, thus mediating
activation or repression of their expression (Milan, 2004).
This study presents evidence that Osa, a member of a subset of Brahma chromatin
remodeling complexes, behaves overall as a general activator of Apterous
activity in the Drosophila wing. Overexpression of Osa rescues and loss of Osa
enhances the Beadex1 phenotype. It does so by
modulating the expression levels of Apterous target genes, some of them being
activated (e.g. Serrate and probably other unknown target genes) and some
repressed (e.g. Delta, fringe). Chip has been shown to bind Osa.
The fact that Osa has different
effects on the transcription of Apterous target genes suggests that Chip
recruits Osa to the promoters and in combination with other unknown factors
mediates either transcriptional repression or activation. Osa mediates
repression of both Apterous dependent and independent expression of
fringe, suggesting a direct and probably Chip independent effect of Osa
on fringe transcription (Milan, 2004).
Apterous activity is regulated during
development by dLMO. Osa is required to mediate repression of dLMO expression.
Since both early and late expression of dLMO
depend on Chip, it is postulated that Chip forms a transcriptional complex with
Apterous in the D compartment and an unknown transcription factor expressed in
the wing pouch. Osa may interact with Chip thus recruiting the Brahma complex to
the dLMO locus and remodeling chromatin in a way that limits dLMO
transcriptional activation. High levels of dLMO protein reduce Apterous activity
and the Notch dependent organizer is not properly induced along the DV boundary.
Osa mediated repression of dLMO expression may ensure moderate levels of
expression of dLMO in the wing, thus allowing proper wing development. Gain of
function mutations that cause misexpression of vertebrate LMO proteins have been
implicated in cancers of the lymphoid system. Truncating mutations in the human
SWI-SNF complex, the human homologues of the Brahma complex, cause various types
of human cancers. The SWI-SNF complex may be required to mediate repression of LMO
expression in lymphoid tissues. Thus, it would be very interesting to analyze if
truncating mutations in members of the human SWI-SNF complex cause higher levels
of LMO expression and are associated with lymphoid malignancies (Milan, 2004).
It has been shown that the Brahma complex plays a general role in transcription by RNA Polymerase II. Then, is Osa having a general effect on the expression levels of every gene involved in wing patterning? Several observations indicate this is not the case. (1) Osa is a component of a subset of Brahma (Brm) chromatin complexes.
(2) Brahma and Polycomb were shown to have non-overlapping binding patterns
in polytenic chromosomes. Those
genes involved in wing patterning and regulated by Polycomb (i.e. Hedgehog) may not be
affected by overexpression of Osa. (3) Overexpression of Osa has different
effects on the expression levels of Serrate, Delta and fringe.
(4) Osa has been shown to specifically regulate
the expression of Wingless target genes and the Achaete-scute complex genes,
interestingly by restricting their expression levels (Milan, 2004).
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Rajaiya, J., et al. (2005). Bruton's tyrosine kinase regulates immunoglobulin promoter activation in association with the transcription factor Bright.
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in Drosophila melanogaster. Genetics 153: 275-287. PubMed Citation: 10471712
Terriente-Félix, A. and de Celis. J. F. (2009). Osa, a subunit of the BAP chromatin-remodelling complex, participates in the regulation of gene expression in response to EGFR signalling in the Drosophila wing. Dev. Biol. 329(2): 350-61. PubMed Citation: 19306864
Treisman, J. E., Luk, A., Rubin, G. M. and Heberlein, U. (1997). eyelid antagonizes wingless signaling during Drosophila development and has homology to the Bright family of DNA-binding proteins. Genes Dev. 11: 1949-1962. PubMed Citation: 9271118
Trouche, D., et al. (1997). RB and hBRM cooperate to repress the activation functions of E2F-1. Proc. Natl. Acad. Sci. 94: 11268-11273. PubMed Citation: 9326598
Vazquez, M., Moore, L. and Kennison, J. A. (1999).
The trithorax group gene osa encodes an ARID-domain protein that
genetically interacts with the Brahma chromatin-remodeling factor to regulate
transcription. Development 126: 733-742. PubMed Citation: 9895321
osa/eyelid:
Biological Overview
| Evolutionary Homologs
| Regulation
| Developmental Biology
| Effects of Mutation
date revised: 1 November 2010
Home page: The Interactive Fly © 1997 Thomas B. Brody, Ph.D.
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