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PMID:20833366

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Citation

Trivedi, CM, Zhu, W, Wang, Q, Jia, C, Kee, HJ, Li, L, Hannenhalli, S and Epstein, JA (2010) Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Dev. Cell 19:450-9

Abstract

Regulation of chromatin structure via histone modification has recently received intense attention. Here, we demonstrate that the chromatin-modifying enzyme histone deacetylase 2 (Hdac2) functions with a small homeodomain factor, Hopx, to mediate deacetylation of Gata4, which is expressed by cardiac progenitor cells and plays critical roles in the regulation of cardiogenesis. In the absence of Hopx and Hdac2 in mouse embryos, Gata4 hyperacetylation is associated with a marked increase in cardiac myocyte proliferation, upregulation of Gata4 target genes, and perinatal lethality. Hdac2 physically interacts with Gata4, and this interaction is stabilized by Hopx. The ability of Gata4 to transactivate cell cycle genes is impaired by Hopx/Hdac2-mediated deacetylation, and this effect is abrogated by loss of Hdac2-Gata4 interaction. These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development.

Links

PubMed PMC2947937 Online version:10.1016/j.devcel.2010.08.012

Keywords

Acetylation; Animals; Biological Markers/metabolism; Blotting, Western; Cell Proliferation; Embryo, Mammalian/metabolism; Fluorescent Antibody Technique; GATA4 Transcription Factor/metabolism; Gene Expression Profiling; Histone Deacetylase 2/physiology; Homeodomain Proteins/physiology; Immunoenzyme Techniques; Immunoprecipitation; In Situ Hybridization; Luciferases/metabolism; Mice; Mice, Knockout; Mutagenesis, Site-Directed; Myocytes, Cardiac/cytology; Myocytes, Cardiac/metabolism; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction

Significance

Annotations

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

MOUSE:HDAC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q08369

F

Seeded From UniProt

complete

MOUSE:GATA4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P70288

F

Seeded From UniProt

complete

MOUSE:HOP

acts_upstream_of_or_within

GO:0043393: regulation of protein binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

acts_upstream_of_or_within

GO:0051091: positive regulation of DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HDAC2

acts_upstream_of_or_within

GO:0090311: regulation of protein deacetylation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916782

P

Seeded From UniProt

complete


See also

References

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