SWI/SNF activity is required for the repression of deoxyribonucleotide triphosphate metabolic enzymes via the recruitment of mSin3B

Ranjaka W. Gunawardena, Sejal R. Fox, Hasan Siddiqui, Erik S. Knudsen

Research output: Contribution to journalArticle

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Abstract

The SWI/SNF chromatin remodeling complex plays a critical role in the coordination of gene expression with physiological stimuli. The synthetic enzymes ribonucleotide reductase, dihydrofolate reductase, and thymidylate synthase are coordinately regulated to ensure appropriate deoxyribonucleotide triphosphate levels. Particularly, these enzymes are actively repressed as cells exit the cell cycle through the action of E2F transcription factors and the retinoblastoma tumor suppressor/p107/p130 family of pocket proteins. This process is found to be highly dependent on SWI/SNF activity as cells deficient in BRG-1 and Brm subunits fail to repress these genes with activation of pocket proteins, and this deficit in repression can be complemented, via the ectopic expression of BRG-1. The failure to repress transcription does not involve a blockade in the association of E2F or pocket proteins p107 and p130 with promoter elements. Rather, the deficit in repression is due to a failure to mediate histone deacetylation of ribonucleotide reductase, dihydrofolate reductase, and thymidylate synthase promoters in the absence of SWI/SNF activity. The basis for this is found to be a failure to recruit mSin3B and histone deacetylase proteins to promoters. Thus, the coordinate repression of deoxyribonucleotide triphosphate metabolic enzymes is dependent on the action of SWI/SNF in facilitating the assembly of repressor complexes at the promoter.

Original languageEnglish (US)
Pages (from-to)20116-20123
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number28
DOIs
StatePublished - Jul 13 2007

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Deoxyribonucleotides
Ribonucleotide Reductases
Enzymes
Proteins
E2F Transcription Factors
Histone Deacetylases
Chromatin Assembly and Disassembly
Retinoblastoma
Transcription
Gene expression
Histones
Transcriptional Activation
Chromatin
Tumors
Cell Cycle
Genes
Chemical activation
Cells
Association reactions
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

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SWI/SNF activity is required for the repression of deoxyribonucleotide triphosphate metabolic enzymes via the recruitment of mSin3B. / Gunawardena, Ranjaka W.; Fox, Sejal R.; Siddiqui, Hasan; Knudsen, Erik S.

In: Journal of Biological Chemistry, Vol. 282, No. 28, 13.07.2007, p. 20116-20123.

Research output: Contribution to journalArticle

Gunawardena, Ranjaka W. ; Fox, Sejal R. ; Siddiqui, Hasan ; Knudsen, Erik S. / SWI/SNF activity is required for the repression of deoxyribonucleotide triphosphate metabolic enzymes via the recruitment of mSin3B. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 28. pp. 20116-20123.
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