Chromosomal localization links the SIN3-RPD3 complex to the regulation of chromatin condensation, histone acetylation and gene expression

Pile, Lori A.; Wassarman, David A.

doi:10.1093/emboj/19.22.6131

Cited by 77 publications

(84 citation statements)

References 86 publications

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“…Overall, these findings are consistent with immunofluorescence staining of Drosophila polytene chromosomes, which revealed that the SIN3 complex binds throughout euchromatic regions but is largely absent from centric heterochromatin and most of the fourth chromosome (19). Similarly, in yeast, RPD3 is excluded from telomeric heterochromatin and sub-telomeric domains (21).…”

Section: Sin3-regulated Genes Tend To Be Excluded From Heterochromatisupporting

confidence: 85%

“…This is likely to be a minimum number of genes regulated by SIN3, because our analysis excluded genes whose expression is altered only in S2 or Kc cells. The number of genes affected by loss of SIN3 is in line with immunofluorescence studies of Drosophila polytene chromosomes, through which it was estimated that 2-13% of Drosophila genes are directly bound by the SIN3 complex (19). The overwhelming majority of the 399 genes had altered expression levels of less than 2-fold, indicating that this group of genes would have been difficult to detect without the analysis of multiple arrays and cell types (see Supplemental data).…”

Section: Sin3 Is a Transcriptionalmentioning

confidence: 52%

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The SIN3 Deacetylase Complex Represses Genes Encoding Mitochondrial Proteins

Pile

Spellman

Katzenberger

et al. 2003

Journal of Biological Chemistry

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Deacetylation of histones by the SIN3 complex is a major mechanism utilized in eukaryotic organisms to repress transcription. Presumably, developmental and cellular phenotypes resulting from mutations in SIN3 are a consequence of altered transcription of SIN3 target genes. Therefore, to understand the molecular mechanisms underlying SIN3 mutant phenotypes in Drosophila, we used full-genome oligonucleotide microarrays to compare gene expression levels in wild type Drosophila tissue culture cells versus SIN3-deficient cells generated by RNA interference. Of the 13,137 genes tested, 364 were induced and 35 were repressed by loss of SIN3. The ϳ10-fold difference between the number of induced and repressed genes suggests that SIN3 plays a direct role in regulating these genes. The identified genes are distributed throughout euchromatic regions but are preferentially excluded from heterochromatic regions of Drosophila chromosomes suggesting that the SIN3 complex can only access particular chromatin structures. A number of cell cycle regulators were repressed by loss of SIN3, and functional studies indicate that repression of string, encoding the Drosophila homologue of the yeast CDC25 phosphatase, contributes to the G 2 cell cycle delay of SIN3-deficient cells. Unexpectedly, a substantial fraction of genes induced by loss of SIN3 is involved in cytosolic and mitochondrial energy-generating pathways and other genes encode components of the mitochondrial translation machinery. Increased expression of mitochondrial proteins in SIN3-deficient cells is manifested in an increase in mitochondrial mass. Thus, SIN3 may play an important role in regulating mitochondrial respiratory activity.

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Section: Sin3-regulated Genes Tend To Be Excluded From Heterochromatisupporting

confidence: 85%

Section: Sin3 Is a Transcriptionalmentioning

confidence: 52%

The SIN3 Deacetylase Complex Represses Genes Encoding Mitochondrial Proteins

Pile

Spellman

Katzenberger

et al. 2003

Journal of Biological Chemistry

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“…Because transcription in polytene chromosomes localizes mostly to the interbands, these results further support the idea that histone phosphorylation, and not acetylation, is widely associated with active transcription in Drosophila. In addition to the dis- tribution of acetylated histones H3 at Lys 14 and H4 at Lys 8 described in this work, identical polytene bandinterband distribution has been found for polyacetylated H3, acetylated H4-Lys 5, and acetylated H4-Lys 12 (Pile and Wassarman 2000). In light of the large amount of evidence suggesting a role for histone acetylation in transcription activation, Pile and Wassarman (2000) interpreted these results as suggesting that immunolocalization on polytene chromosomes might not be sufficiently sensitive to detect changes in histone acetylation after transcription initiation, and that the pattern of histone acetylation along the chromosome might be a reflection of background acetylation, only visible in polytene bands where chromatin is highly compacted.…”

Section: Transcription Of Gal4-activated Transgenes Is Independent Ofsupporting

confidence: 82%

Phosphorylation of histone H3 during transcriptional activation depends on promoter structure

Labrador¹,

Corcés²

2003

Genes Dev.

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Covalent modifications of histone N-terminal tails are required for the proper assembly and activation of the general transcription factors at promoters. Here, we analyze histone acetylation and phosphorylation in Drosophila transgenes activated by the yeast Gal4 transcriptional activator in the context of different promoters. We show that, independent of the promoter, transcription does not correlate with acetylation of either H3-Lys 14 or H4-Lys 8. Histone H3 associated with the DNA of Gal4-induced transcribing transgenes driven by the Drosophila Hsp70 promoter is hyperphosphorylated at Ser 10 during transcription. Surprisingly, histone H3 at Gal4-induced transgenes driven by the P element Transposase promoter is not hyperphosphorylated. The data suggest that transcription occurs without acetylated H4 and H3 in both transgenes in Drosophila polytene chromosomes. Instead, phosphorylation of H3 is linked to transcription and can be modulated by the structure of the promoter. Received July 8, 2002; revised version accepted October 31, 2002. Posttranslational covalent modifications of N-terminal tails of the core histones at the nucleosome play an important role in determining chromatin structure, which is an essential component of the control of nuclear biology (Jenuwein and Allis 2001). The expression of a large number of genes from organisms across the phylogenetic scale correlates with histone modifications such as acetylation, methylation, phosphorylation, and ubiquitination in the nucleosomes surrounding the promoter of the gene (Roth et al. 2001;Berger 2002;Fry and Peterson 2002;Sun and Allis 2002). Acetylation of histones H3 and H4 N-terminal tails has been broadly associated with activation of transcription. Histone acetyl-transferases (HATs) are found in a variety of coactivators and transcription factor complexes, whereas histone deacetylases (HDACs) are present in protein complexes with a repressive function (Roth et al. 2001). H3 methylation at Lys 9 has the opposite effect and therefore is found in regions where transcription is repressed by chromatin structure (Rea et al. 2000;Bannister et al. 2001). Phosphorylation of H3 at Ser 10 has also been correlated with activation of transcription in yeast, mammals, and Drosophila (Cheung et al. 2000;Lo et al. 2000;Nowak and Corces 2000;Lo et al. 2001;Thomson et al. 2001;Li et al. 2002;Strelkov and Davie 2002).Two nonexclusive models have been postulated to explain the role of histone N-terminal tail modification in transcription. The first one suggests that histone modifications have an effect on the relative charge of the histone tails, rendering a more open or closed chromatin state that determines the accessibility of transcription factors to the core promoter. The second model, termed the histone code hypothesis, predicts that a combination of covalent modifications of histone tails functions as a target for the specific binding of effector proteins (Turner 2000;Jenuwein and Allis 2001). Binding of these proteins will ultimately determine the transc...

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“…Furthermore, HDAC1 is much more widely distributed along the chromosomes than is PSC (Fig. 4), consistent with its role in global gene regulation and͞or chromatin structure (41)(42)(43)(44).…”

Section: Colocalization Of Hdac1 and Pc-g Proteins On Polytene Chromosupporting

confidence: 57%

“…It is possible that an adapter-like molecule might be involved. In several organisms, direct interactions or cytological colocalization between HDAC1 and SIN3A proteins has been demonstrated (24,44). However, there is currently no evidence that SIN3A is required for homeotic gene repression.…”

Section: Discussionmentioning

confidence: 99%

Essential role of Drosophila Hdac1 in homeotic gene silencing

Chang

Peng

Pan

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Deacetylation of the N-terminal tails of core histones plays a crucial role in gene silencing. Rpd3 and Hda1 represent two major types of genes encoding trichostatin A-sensitive histone deacetylases. Although they have been widely found, their cellular and developmental roles remain to be elucidated in metazoa. We show that Drosophila Hdac1, an Rpd3-type gene, interacts cooperatively with Polycomb group repressors in silencing the homeotic genes that are essential for axial patterning of body segments. The biochemical copurification and cytological colocalization of HDAC1 and Polycomb group repressors strongly suggest that HDAC1 is a component of the silencing complex for chromatin modification on specific regulatory regions of homeotic genes.Pc-G ͉ histone deacetylase ͉ Ubx ͉ PRE

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Chromosomal localization links the SIN3-RPD3 complex to the regulation of chromatin condensation, histone acetylation and gene expression

Cited by 77 publications

References 86 publications

The SIN3 Deacetylase Complex Represses Genes Encoding Mitochondrial Proteins

The SIN3 Deacetylase Complex Represses Genes Encoding Mitochondrial Proteins

Phosphorylation of histone H3 during transcriptional activation depends on promoter structure

Essential role of Drosophila Hdac1 in homeotic gene silencing

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