Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis.
Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis.
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DOI：
10.1016/j.ydbio.2017.11.017
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发表时间：
2018-02-01
影响因子：
2.7
通讯作者：
Hoppler S
中科院分区：
文献类型：
--
作者：
Afouda BA;Lynch AT;de Paiva Alves E;Hoppler S
转录因子GATA 4、GATA 5和GATA 6是心肌分化（心肌发生）的重要调节因子，其以部分冗余的方式起作用。我们在全基因组转录组学分析中确定了由单个心源性加塔因子特异性调控的基因。由gata 4调控的基因特别有趣，因为GATA 4能够诱导爪蟾和哺乳动物系统中搏动心肌细胞的分化。在gata 4特异性调节的转录本中，我们鉴定出了两个SoxF家族成员，sox 7和sox 18。实验性恢复gata 4可恢复sox 7和sox 18的表达，而由于gata 4敲低而导致的心肌细胞分化的丧失可通过恢复sox 7或sox 18的表达而部分恢复，同时（如先前报道的）敲低sox 7或sox 18会干扰心肌形成。为了测试哺乳动物心肌发生中的保守性，我们在经历心肌发生的小鼠胚胎干细胞（ESC）中证实Gata 4的敲低导致Sox 7（和Sox 18）表达减少，并且Gata 4也独特地能够迅速诱导Sox 7表达。两者合计，我们确定了一个重要的和保守的基因调控轴从gata 4到SoxF旁系同源物sox 7和sox 18，并进一步心肌细胞分化。加塔4、5和6在心脏发育中具有冗余和非冗余功能。进行Gata 4、5和6敲低实验的RNA-seq分析。鉴定了Gata 4、5和6特异性调控的基因。SoxF基因sox 7和sox 18被鉴定为受Gata 4特异性调控。上位性表明从Gata 4到Sox 7/18到心肌发生的调节轴。
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. Gata 4, 5 and 6 have redundant and non-redundant functions in heart development. RNA-seq analysis of Gata4, 5 and 6 knockdown experiments was carried out. Genes specifically regulated by Gata4, 5 and 6 were identified. The SoxF genes sox7 and sox18 were identified as specifically regulated by Gata4. Epistasis demonstrates a regulatory axis from Gata4 to Sox7/18 to cardiomyogenesis.
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