FOXC1 Downregulates Nanog Expression by Recruiting HDAC2 to Its Promoter in F9 Cells Treated by Retinoic Acid.
FOXC1 Downregulates Nanog Expression by Recruiting HDAC2 to Its Promoter in F9 Cells Treated by Retinoic Acid.
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在视黄酸处理的 F9 细胞中，FOXC1 通过将 HDAC2 招募至其启动子来下调 Nanog 表达
DOI：
10.3390/ijms22052255
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发表时间：
2021-02-24
影响因子：
5.6
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Xue H;Liu F;Ai Z;Ke J;Yu M;Chen B;Guo Z
FOXC 1是一种参与细胞分化和胚胎发生的转录因子，在这项研究中被证明是Nanog的负调控因子。FOXC 1在视黄酸诱导的F9胚胎癌（EC）细胞分化中上调;此外，FOXC 1通过与近端启动子结合特异性抑制核心多能性因子Nanog。F9中FOXC 1的过表达或3T3中FOXC 1的敲低分别导致Nanog mRNA和蛋白的下调或上调。为了解释FOXC 1抑制Nanog表达的机制，我们从FOXC 1相互作用组中鉴定了共阻遏物HDAC 2。FOXC 1将HDAC 2募集到Nanog启动子以减少H3K27ac富集，导致Nanog的转录抑制。据我们所知，这是第一次报道FOXC 1参与基因表达的表观遗传调控。
FOXC1, a transcription factor involved in cell differentiation and embryogenesis, is demonstrated to be a negative regulator of Nanog in this study. FOXC1 is up-regulated in retinoic acid-induced differentiation of F9 Embryonal Carcinoma (EC) cells; furthermore, FOXC1 specifically inhibits the core pluripotency factor Nanog by binding to the proximal promoter. Overexpression of FOXC1 in F9 or knockdown in 3T3 results in the down-regulation or up-regulation of Nanog mRNA and proteins, respectively. In order to explain the mechanism by which FOXC1 inhibits Nanog expression, we identified the co-repressor HDAC2 from the FOXC1 interactome. FOXC1 recruits HDAC2 to Nanog promoter to decrease H3K27ac enrichment, resulting in transcription inhibition of Nanog. To the best of our knowledge, this is the first report that FOXC1 is involved in the epigenetic regulation of gene expression.
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