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PMID:21832073

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Citation

Eom, GH, Kim, KB, Kim, JH, Kim, JY, Kim, JR, Kee, HJ, Kim, DW, Choe, N, Park, HJ, Son, HJ, Choi, SY, Kook, H and Seo, SB (2011) Histone methyltransferase SETD3 regulates muscle differentiation. J. Biol. Chem. 286:34733-42

Abstract

Histone lysine methylation, as one of the most important factors in transcriptional regulation, is associated with a various physiological conditions. Using a bioinformatics search, we identified and subsequently cloned mouse SET domain containing 3 (SETD3) with SET (Su(var)3-9, Enhancer-of-zeste and Trithorax) and Rubis-subs-bind domains. SETD3 is a novel histone H3K4 and H3K36 methyltransferase with transcriptional activation activity. SETD3 is expressed abundantly in muscular tissues and, when overexpressed, activates transcription of muscle-related genes, myogenin, muscle creatine kinase (MCK), and myogenic factor 6 (Myf6), thereby inducing muscle cell differentiation. Conversely, knockdown of SETD3 by shRNA significantly retards muscle cell differentiation. In this study, SETD3 was recruited to the myogenin gene promoter along with MyoD where it activated transcription. Together, these data indicate that SETD3 is a H3K4/K36 methyltransferase and plays an important role in the transcriptional regulation of muscle cell differentiation.

Links

PubMed PMC3186363 Online version:10.1074/jbc.M110.203307

Keywords

Animals; Cell Differentiation; Chromatin/chemistry; Computational Biology/methods; Gene Expression Regulation; Histone-Lysine N-Methyltransferase/chemistry; Histone-Lysine N-Methyltransferase/physiology; Histones/chemistry; Mice; Muscles/metabolism; Myogenin/chemistry; Plasmids/metabolism; Protein Conformation; Rats; Transcription, Genetic; Transfection

Significance

Annotations

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

MOUSE:MYOD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91WC0

F

Seeded From UniProt

complete

MOUSE:MYOD1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1289184

P

  • has_input:(MGI:MGI:97276)

Seeded From UniProt

complete

MOUSE:SETD3

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SETD3

enables

GO:0042800: histone methyltransferase activity (H3-K4 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SETD3

enables

GO:0046975: histone methyltransferase activity (H3-K36 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SETD3

acts_upstream_of_or_within

GO:0051149: positive regulation of muscle cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SETD3

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SETD3

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:97275

P

  • has_input:(MGI:MGI:97276)

Seeded From UniProt

complete

MOUSE:SETD3

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P10085

F

Seeded From UniProt

complete

MOUSE:MYOD1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1289184

P

has_regulation_target:(MGI:MGI:97276)

Seeded From UniProt

complete


See also

References

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