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Dev Biol 2018 Feb 01;4341:108-120. doi: 10.1016/j.ydbio.2017.11.017.
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Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis.

Afouda BA , Lynch AT , de Paiva Alves E , Hoppler S .

The transcription factors GATA4, GATA5 and GATA6 are important regulators of heart muscle differentiation (cardiomyogenesis), which function in a partially redundant manner. We identified genes specifically regulated by individual cardiogenic GATA factors in a genome-wide transcriptomics analysis. The genes regulated by gata4 are particularly interesting because GATA4 is able to induce differentiation of beating cardiomyocytes in Xenopus and in mammalian systems. Among the specifically gata4-regulated transcripts we identified two SoxF family members, sox7 and sox18. Experimental reinstatement of gata4 restores sox7 and sox18 expression, and loss of cardiomyocyte differentiation due to gata4 knockdown is partially restored by reinstating sox7 or sox18 expression, while (as previously reported) knockdown of sox7 or sox18 interferes with heart muscle formation. In order to test for conservation in mammalian cardiomyogenesis, we confirmed in mouse embryonic stem cells (ESCs) undergoing cardiomyogenesis that knockdown of Gata4 leads to reduced Sox7 (and Sox18) expression and that Gata4 is also uniquely capable of promptly inducing Sox7 expression. Taken together, we identify an important and conserved gene regulatory axis from gata4 to the SoxF paralogs sox7 and sox18 and further to heart muscle cell differentiation.

PubMed ID: 29229250
PMC ID: PMC5814753
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adamts10 adamts3 armc8 asb15 asb4 b3galt2l cacnb2 cdk2ap1 clvs1 cuta cxxc4 eno3 f2rl3 fdxr fli1 gata4 gata5 gata6 hck ift74 isl1 lrch4 mafb mef2c mespa mespb mocs2 mpdu1 myl2 nfatc4 nrbp2 nup88 ocm4.5 pck2 pcp4l1 pcyt1a ppp1r9b prelid2 qdpr qrfpr sbk1 sez6 slc23a3 sox18 sox7 spry3 swsap1 syt1 tbx5 tdp1 tgfb1 tnni3 tnnt2 tor1b tubb3 vrk1 XB992002
GO keywords: heart development
Morpholinos: gata4 MO4 gata5 MO4 gata6 MO1 gata6 MO2 sox18 MO1 sox7 MO1

Disease Ontology terms: congenital heart disease
Phenotypes: Xla.Tg(myl2:GFP){Mohun} + gata4 MO + Activin + explant (Fig.1 CD) [+]

Article Images: [+] show captions
References [+] :
Afouda, Different requirements for GATA factors in cardiogenesis are mediated by non-canonical Wnt signaling. 2011, Pubmed, Xenbase