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A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.

Molecular cell | Aug 17, 2007

Deciphering the epigenetic "code" remains a central issue in transcriptional regulation. Here, we report the identification of a JAMM/MPN(+) domain-containing histone H2A deubiquitinase (2A-DUB, or KIAA1915/MYSM1) specific for monoubiquitinated H2A (uH2A) that has permitted delineation of a strategy for specific regulatory pathways of gene activation. 2A-DUB regulates transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. 2A-DUB interacts with p/CAF in a coregulatory protein complex, with its deubiquitinase activity modulated by the status of acetylation of nucleosomal histones. Consistent with this mechanistic role, 2A-DUB participates in transcriptional regulation events in androgen receptor-dependent gene activation, and the levels of uH2A are dramatically decreased in prostate tumors, serving as a cancer-related mark. We suggest that H2A ubiquitination represents a widely used mechanism for many regulatory transcriptional programs and predict that various H2A ubiquitin ligases/deubiquitinases will be identified for specific cohorts of regulated transcription units.

Pubmed ID: 17707232 RIS Download

Mesh terms: Acetylation | Androgens | Animals | Cell Line | Chromatography, Affinity | DNA-Binding Proteins | Gene Expression Regulation | Histone Acetyltransferases | Histones | Humans | Mice | Models, Genetic | Nucleosomes | Phosphorylation | Receptors, Androgen | Signal Transduction | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Ubiquitins

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R37 DK039949
  • Agency: NHLBI NIH HHS, Id: R01 HL065445
  • Agency: NHLBI NIH HHS, Id: R01 HL065445-09
  • Agency: NINDS NIH HHS, Id: R01 NS048243
  • Agency: NIDDK NIH HHS, Id: R37 DK039949-27
  • Agency: NINDS NIH HHS, Id: R01 NS048243-03

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