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PMID:18157086

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Citation

Edmunds, JW, Mahadevan, LC and Clayton, AL (2008) Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 27:406-20

Abstract

Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. We produced high-resolution comparative maps of the distribution and dynamics of H3K4me3, H3K36me3, H3K79me2 and H3K9ac across c-fos and c-jun upon gene induction in murine fibroblasts. In unstimulated cells, continuous turnover of H3K9 acetylation occurs on all K4-trimethylated histone H3 tails; distribution of both modifications coincides across promoter and 5' part of the coding region. In contrast, K36- and K79-methylated H3 tails, which are not dynamically acetylated, are restricted to the coding regions of these genes. Upon stimulation, transcription-dependent increases in H3K4 and H3K36 trimethylation are seen across coding regions, peaking at 5' and 3' ends, respectively. Addressing molecular mechanisms involved, we find that Huntingtin-interacting protein HYPB/Setd2 is responsible for virtually all global and transcription-dependent H3K36 trimethylation, but not H3K36-mono- or dimethylation, in these cells. These studies reveal four distinct layers of histone modification across inducible mammalian genes and show that HYPB/Setd2 is responsible for H3K36 trimethylation throughout the mouse nucleus.

Links

PubMed PMC2168397 Online version:10.1038/sj.emboj.7601967

Keywords

Animals; Blotting, Northern; Cell Line; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Epidermal Growth Factor/pharmacology; Gene Expression Regulation; Histones/metabolism; Immunoblotting; Immunoprecipitation; Lysine/metabolism; Methylation/drug effects; Mice; Mice, Inbred C3H; Proto-Oncogene Proteins c-fos/genetics; Proto-Oncogene Proteins c-fos/metabolism; Proto-Oncogene Proteins c-jun/genetics; Proto-Oncogene Proteins c-jun/metabolism; RNA, Small Interfering/genetics; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic/drug effects; Transcriptional Activation; Transfection

Significance

Annotations

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

MOUSE:SETD2

located_in

GO:0005694: chromosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SETD2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SETD2

involved_in

GO:0018023: peptidyl-lysine trimethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SETD2

involved_in

GO:0010452: histone H3-K36 methylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NSD1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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