GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17991879

From GONUTS
Jump to: navigation, search
Citation

Lockman, K, Taylor, JM and Mack, CP (2007) The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression. Circ. Res. 101:e115-23

Abstract

We and others have previously shown that the myocardin transcription factors play critical roles in the regulation of smooth muscle cell (SMC) differentiation marker gene expression. In a yeast 2-hybrid screen for proteins that interact with myocardin-related transcription factor-A (MRTF-A), we identified the histone 3 lysine 9 (H3K9)-specific demethylase, Jmjd1a. GST pull-down assays demonstrated that Jmjd1a bound all 3 myocardin family members, and further mapping studies showed that the jumonjiC domain of Jmjd1a was sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreased global levels of di-methyl H3K9, stimulated the SM alpha-actin and SM22 promoters, and synergistically enhanced MRTF-A- and myocardin-dependent transactivation. Using chromatin immunoprecipitation assays, we also demonstrated that TGF-beta-mediated upregulation of SMC differentiation marker gene expression in 10T1/2 cells was associated with decreased H3K9 dimethylation at the CArG-containing regions of the SMC differentiation marker gene promoters. Importantly, knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic SMCs by retroviral delivery of siRNA attenuated TGF-beta-induced upregulation of endogenous SM myosin heavy chain expression. These effects were concomitant with increased H3K9 dimethylation at the SMC differentiation marker gene promoters and with inhibition of MRTF-A-dependent transactivation of the SMC-specific transcription. These results suggest, for the first time, that SMC differentiation marker gene expression is regulated by H3K9 methylation and that the effects of the myocardin factors on SMC-specific transcription may involve the recruitment of Jmjd1a to the SMC-specific promoters.

Links

PubMed Online version:10.1161/CIRCRESAHA.107.164178

Keywords

Animals; Biological Markers/metabolism; Cell Differentiation/genetics; Cells, Cultured; Gene Expression Regulation/physiology; Histones/metabolism; Jumonji Domain-Containing Histone Demethylases; Mice; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/enzymology; Myocytes, Smooth Muscle/cytology; Myocytes, Smooth Muscle/enzymology; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Oxidoreductases, N-Demethylating/metabolism; Rats; Trans-Activators/genetics; Trans-Activators/metabolism

Significance

Annotations

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

MOUSE:MRTFB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6PCM1

F

Seeded From UniProt

complete

MOUSE:MRTFB

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MRTFB

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:KDM3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8VIM5

F

Seeded From UniProt

complete

MOUSE:KDM3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8K4J6

F

Seeded From UniProt

complete

MOUSE:KDM3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P59759

F

Seeded From UniProt

complete

MOUSE:KDM3A

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KDM3A

enables

GO:0003712: transcription coregulator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KDM3A

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:KDM3A

acts_upstream_of_or_within

GO:0036123: histone H3-K9 dimethylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM3A

acts_upstream_of_or_within

GO:0036123: histone H3-K9 dimethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MRTFA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6PCM1

F

Seeded From UniProt

complete

MOUSE:MRTFA

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MRTFA

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MRTFA

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:MYCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6PCM1

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.