The SIN3 deacetylase complex represses genes encoding mitochondrial proteins: Implications for the regulation of energy metabolism

Lori A. Pile, Paul Spellman, Rebeccah J. Katzenberger, David A. Wassarman

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 ∼10-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 G2 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.

Original languageEnglish (US)
Pages (from-to)37840-37848
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number39
DOIs
StatePublished - Sep 26 2003
Externally publishedYes

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Sin3 Histone Deacetylase and Corepressor Complex
Gene encoding
Mitochondrial Proteins
Energy Metabolism
Genes
Drosophila
Cell Cycle
Transcription
Gene Components
Phenotype
Cells
RNA Interference
Oligonucleotide Array Sequence Analysis
Phosphoric Monoester Hydrolases
Tissue culture
Histones
Chromatin
Microarrays
Chromosomes
Cell Culture Techniques

ASJC Scopus subject areas

  • Biochemistry

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The SIN3 deacetylase complex represses genes encoding mitochondrial proteins : Implications for the regulation of energy metabolism. / Pile, Lori A.; Spellman, Paul; Katzenberger, Rebeccah J.; Wassarman, David A.

In: Journal of Biological Chemistry, Vol. 278, No. 39, 26.09.2003, p. 37840-37848.

Research output: Contribution to journalArticle

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