PMID:20833366

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
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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

References

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