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PMID:18172164

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Citation

Nakagawa, T, Kajitani, T, Togo, S, Masuko, N, Ohdan, H, Hishikawa, Y, Koji, T, Matsuyama, T, Ikura, T, Muramatsu, M and Ito, T (2008) Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. Genes Dev. 22:37-49

Abstract

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation.

Links

PubMed PMC2151013 Online version:10.1101/gad.1609708

Keywords

Animals; Chromatin/metabolism; Chromatin Immunoprecipitation; Histone Deacetylases/metabolism; Histones/chemistry; Histones/metabolism; Lysine/metabolism; Methylation; Mice; Models, Biological; Models, Genetic; Transcription Initiation Site; Transcriptional Activation; Ubiquitin/metabolism; Ubiquitin Thiolesterase/metabolism; Ubiquitination/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KMT2C

involved_in

GO:0016571: histone methylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:UBP21

involved_in

GO:0016578: histone deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:UBP21

located_in

GO:0005634: nucleus

ECO:0000305: curator inference used in manual assertion

GO:0016578

C

Seeded From UniProt

complete

MOUSE:UBP21

enables

GO:0008234: cysteine-type peptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:UBP21

enables

GO:0004843: thiol-dependent deubiquitinase

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:UBP21

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:UBP21

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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