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PMID:18157086
| 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 |
| edit table |
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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