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首页> 外文期刊>Journal of Molecular Biology >CARM1 (PRMT4) Acts as a Transcriptional Coactivator during Retinoic Acid-Induced Embryonic Stem Cell Differentiation
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CARM1 (PRMT4) Acts as a Transcriptional Coactivator during Retinoic Acid-Induced Embryonic Stem Cell Differentiation

机译：CARM1（PRMT4）在视黄酸诱导的胚胎干细胞分化期间用作转录共酰变剂

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Activation of the retinoic acid (RA) signaling pathway is important for controlling embryonic stem cell differentiation and development. Modulation of this pathway occurs through the recruitment of different epigenetic regulators at the retinoic acid receptors (RARs) located at RA-responsive elements and/or RA-responsive regions of RA-regulated genes. Coactivator-associated arginine methyltransferase 1 (CARM1, PRMT4) is a protein arginine methyltransferase that also functions as a transcriptional coactivator. Previous studies highlight CARM1's importance in the differentiation of different cell types. We address CARM1 function during RA-induced differentiation of murine embryonic stem cells (mESCs) using shRNA lentiviral transduction and CRISPR/Cas9 technology to deplete CARM1 in mESCs. We identify CARM1 as a novel transcriptional coactivator required for the RA-associated decrease in Rex1 (Zfp42) and for the RA induction of a subset of RA-regulated genes, includingCRABP2andNR2F1(Coup-TF1). Furthermore, CARM1 is required for mESCs to differentiate into extraembryonic endoderm in response to RA. We next characterize the epigenetic mechanisms that contribute to RA-induced transcriptional activation ofCRABP2andNR2F1in mESCs and show for the first time that CARM1 is required for this activation. Collectively, our data demonstrate that CARM1 is required for transcriptional activation of a subset of RA target genes, and we uncover changes in the recruitment of Suz12 and the epigenetic H3K27me3 and H3K27ac marks at gene regulatory regions forCRABP2andNR2F1during RA-induced differentiation.
机译：维甲酸（RA）信号通路的活化对于控制胚胎干细胞分化和发育是重要的。通过在位于Ra-Crougupe基因的RA响应元素和/或RA响应区域的视黄酸受体（Rars）处的不同表观遗传调节剂的募集来发生该途径的调节。 CaCtivator相关的精氨酸甲基转移酶1（CARM1，PRMT4）是蛋白质精氨酸甲基转移酶，其也用作转录共膜剂。以前的研究突出了CARM1在不同细胞类型的分化中的重要性。我们使用ShRNA慢病毒转导和CRISPR / CAS9技术在鼠胚胎干细胞（MESCS）分化期间地址CARM1功能在MESCS中消耗CARM1。我们将CARM1鉴定为REX1（ZFP42）的RA相关降低以及RA调节基因的子集的RA相关降低所需的新型转录同型试镜，包括RA-CURMUPEN基因的诱导，包括CCRABP2ANDNR2F1（COUP-TF1）。此外，MESC需要CARM1，以响应RA分化为Imoreembryonic EndoDerm。接下来，我们的表征表征致表态遗传机制，其有助于RA诱导的转录激活，并在该激活所需的首次表现出CARM1的第一次。统称，我们的数据表明CARM1是RA靶基因子集的转录激活所必需的，并且我们在基因调节区促进SUZ12和表观遗传学H3K27ME3和H3K27Ac标记的变化，致癌2dR2F1诱导的分化。

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