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Proc Natl Acad Sci U S A 2014 Jan 28;1114:1415-20. doi: 10.1073/pnas.1312993111.
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Cyclin D2 is a GATA4 cofactor in cardiogenesis.

Yamak A , Latinkic BV , Dali R , Temsah R , Nemer M .

The G1 cyclins play a pivotal role in regulation of cell differentiation and proliferation. The mechanisms underlying their cell-specific roles are incompletely understood. Here, we show that a G1 cyclin, cyclin D2 (CycD2), enhances the activity of transcription factor GATA4, a key regulator of cardiomyocyte growth and differentiation. GATA4 recruits CycD2 to its target promoters, and their interaction results in synergistic activation of GATA-dependent transcription. This effect is specific to CycD2 because CycD1 is unable to potentiate activity of GATA4 and is CDK-independent. GATA4 physically interacts with CycD2 through a discreet N-terminal activation domain that is essential for the cardiogenic activity of GATA4. Human mutations in this domain that are linked to congenital heart disease interfere with CycD2-GATA4 synergy. Cardiogenesis assays in Xenopus embryos indicate that CycD2 enhances the cardiogenic function of GATA4. Together, our data uncover a role for CycD2 as a cardiogenic coactivator of GATA4 and suggest a paradigm for cell-specific effects of cyclin Ds.

PubMed ID: 24474767
PMC ID: PMC3910654
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus
Genes referenced: a2m acta2 actl6a ccnd1 ccnd2 cdk4 cdk6 gata1 gata4 gata5 hba1 mapk1 myh6 myl6 myl7 nppa odc1 tbx5

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References [+] :
Angelis, A cyclin D2-Rb pathway regulates cardiac myocyte size and RNA polymerase III after biomechanical stress in adult myocardium. 2008, Pubmed