Heterochromatin: silence is golden.
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Animals↗
Biomedical subjects
Sarah C R Elgin
Publications and source records attributed to Sarah C R Elgin.
The capacity to form H-DNA cannot substitute for GAGA factor binding to a (CT)n*(GA)n regulatory site.
Previous studies of the Drosophila melanogaster hsp26 gene promoter have demonstrated the importance of a homopurine*homopyrimidine segment [primarily (CT)n*(GA)n] for chromatin structure formation and gene activation. (CT)n regions are known to bind GAGA factor, a dominant enhancer of PEV thought to play a role in generating an accessible chromatin structure. The (CT)n region can also form an H-DNA structure in vitro under acidic pH and negative supercoiling; a detailed map of that structure is reported here. To test whether the (CT)n sequence can function through H-DNA in vivo, we have analyzed a series of hsp26-lacZ transgenes with altered sequences in this region. The results indicate that a 25 bp mirror repeat within the homopurine.homopyrimidine region, while adequate for H-DNA formation, is neither necessary nor sufficient for positive regulation of hsp26 when GAGA factor-binding sites have been eliminated. The ability to form H-DNA cannot substitute for GAGA factor binding to the (CT)n sequence.
Animals↗
Heterochromatin protein 2 (HP2), a partner of HP1 in Drosophila heterochromatin.
Heterochromatin protein 1 (HP1), first discovered in Drosophila melanogaster, is a highly conserved chromosomal protein implicated in both heterochromatin formation and gene silencing. We report here characterization of an HP1-interacting protein, heterochromatin protein 2 (HP2), which codistributes with HP1 in the pericentric heterochromatin. HP2 is a large protein with two major isoforms of approximately 356 and 176 kDa. The smaller isoform is produced from an alternative splicing pattern in which two exons are skipped. Both isoforms contain the domain that interacts with HP1; the larger isoform contains two AT-hook motifs. Mutations recovered in HP2 act as dominant suppressors of position effect variegation, confirming a role in heterochromatin spreading and gene silencing.
AT Rich Sequence↗
Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects.
Recent results from diverse organisms point to a self-reinforcing network of interactions among the three best-characterized covalent modifications that mark heterochromatin: histone hypoacetylation, histone H3-Lys9 methylation, and cytosine methylation. These modification systems suggest a mechanistic basis for spreading of heterochromatin over large domains and for stable epigenetic inheritance of the silent state. All three modifications used in packaging heterochromatin are also used in stable silencing of euchromatic genes.
Acetylation↗
Chromosome and expression mechanisms: a year dominated by histone modifications, transitory and remembered.
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Animals↗
Heterochromatin: new possibilities for the inheritance of structure.
Significant portions of the eukaryotic genome are heterochromatic, made up largely of repetitious sequences and possessing a distinctive chromatin structure associated with gene silencing. New insights into the form of packaging, the associated histone modifications, and the associated nonhistone chromosomal proteins of heterochromatin have suggested a mechanism for providing an epigenetic mark that allows this distinctive chromatin structure to be maintained following replication and to spread within a given domain.
Animals↗
GAGA factor and the TFIID complex collaborate in generating an open chromatin structure at the Drosophila melanogaster hsp26 promoter.
The upstream regulatory region of the Drosophila melanogaster hsp26 gene includes two DNase I-hypersensitive sites (DH sites) that encompass the critical heat shock elements. This chromatin structure is required for heat shock-inducible expression and depends on two (CT)n*(GA)n elements bound by GAGA factor. To determine whether GAGA factor alone is sufficient to drive formation of the DH sites, we have created flies with an hsp26/lacZ transgene wherein the entire DNA segment known to interact with the TFIID complex has been replaced by a random sequence. The replacement results in a loss of heat shock-inducible hsp26 expression and drastically diminishes nuclease accessibility in the chromatin of the regulatory region. Chromatin immunoprecipitation experiments show that the decrease in TFIID binding does not reduce GAGA factor binding. In contrast, the loss of GAGA factor binding resulting from (CT)n mutations decreases TFIID binding. These data suggest that both GAGA factor and TFIID are necessary for formation of the appropriate chromatin structure at the hsp26 promoter and predict a regulatory mechanism in which GAGA factor binding precedes and contributes to the recruitment of TFIID.
Animals↗