Wnt-promoted Isl1 expression through a novel TCF/LEF1 binding site and H3K9 acetylation in early stages of cardiomyocyte differentiation of P19CL6 cells
Wnt-promoted Isl1 expression through a novel TCF/LEF1 binding site and H3K9 acetylation in early stages of cardiomyocyte differentiation of P19CL6 cells
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Wnt 在 P19CL6 细胞心肌细胞分化早期通过新的 TCF/LEF1 结合位点和 H3K9 乙酰化促进 Isl1 表达
DOI：
10.1007/s11010-014-2001-y
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发表时间：
2014-03
影响因子：
4.3
通讯作者：
Zhou, Chunyan
中科院分区：
文献类型：
--
作者：
Jia, Zhuqing;Chen, Ping;Ma, Kangtao;Zhou, Chunyan
胰岛1（Islet 1，ISL 1）是第二心脏区域祖细胞的标志物，在心肌细胞分化和增殖中起着至关重要的作用。然而，对Isl 1基因表达的转录调控机制知之甚少。最近的研究表明，Wnt/β-catenin信号在心脏发育过程中调节Isl 1的表达。然而，详细的机制仍不清楚。在本研究中，在我们首次证实Wnt/β-catenin信号部分通过Isl 1激活促进心肌细胞分化之后，我们在P19 CL 6向心肌细胞分化期间进行，探索了Wnt/β-catenin介导的Isl 1表达的潜在调控机制。我们发现了一个新的TCF/LEF 1结合位点，位于2300 bp的上游的Isl 1 ATG。此外，Wnt/β-catenin信号上调组蛋白H3 K9在Isl 1启动子上的TCF/LEF 1结合位点上的乙酰化，导致Isl 1表达上调。这种Wnt介导的H3 K9在Isl 1启动子上的乙酰化通过乙酰转移酶CREB结合蛋白（CBP）而不是p300通过与β-连环蛋白的相互作用来调节。总的来说，这些结果表明，在心肌细胞分化的早期阶段，Wnt/β-catenin信号通过两种方式促进Isl 1表达：新的TCF/LEF 1结合位点和CBP在Isl 1启动子上进行的H3 K9乙酰化。据我们所知，这是首次报道Wnt/β-catenin调节H3 K9靶基因启动子乙酰化的研究。本研究为Wnt介导的Isl 1在心肌细胞分化过程中的转录调控机制提供了新的见解。
Islet 1 (ISL1), a marker of second heart field progenitors, plays a crucial role in cardiomyocyte differentiation and proliferation. However, little is known about transcriptional regulating mechanisms on Isl1 gene expression. Recent studies have demonstrated that Wnt/β-catenin signaling regulates Isl1 expression during heart development. However, the detailed mechanisms still remain unclear. In the present study performed during differentiation of P19CL6 into cardiomyocytes, we explored the underlying regulating mechanisms on Wnt/β-catenin-mediated Isl1 expression after we first confirmed that Wnt/β-catenin signaling promoted cardiomyocyte differentiation partly through Isl1 activation. We found a novel TCF/LEF1 binding site that was located 2300 bp upstream of the Isl1 ATG. Furthermore, Wnt/β-catenin signaling upregulated histone H3K9 acetylation on TCF/LEF1 binding sites on the Isl1 promoter, resulting in upregulation of Isl1 expression. This Wnt-mediated H3K9 acetylation on the Isl1 promoter was modulated by the acetyltransferase CREB-binding protein (CBP), instead of p300, through interaction with β-catenin. Collectively, these results suggest that in early stages of cardiomyocyte differentiation Wnt/β-catenin signaling promotes Isl1 expression via two ways: a novel TCF/LEF1 binding site and H3K9 acetylation conducted by CBP on the Isl1 promoter. To our knowledge, this is the first study reporting Wnt/β-catenin-regulated H3K9 acetylation on promoters of its target genes. And this study gives new insights into transcriptional regulating mechanisms of Wnt-mediated Isl1 expression during cardiomyocyte differentiation.
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影响因子：
4.8
作者：
Moretti, Alessandra;Bellin, Milena;Laugwitz, Karl-Ludwig
通讯作者：
Laugwitz, Karl-Ludwig
影响因子：
1.6
作者：
Cresci, Monica;Vecoli, Cecilia;Andreassi, Maria Grazia
通讯作者：
Andreassi, Maria Grazia
影响因子：
64.8
作者：
K. Laugwitz;A. Moretti;J. Lam;P. Gruber;Y. Chen;S. Woodard;L. Lin;C. Cai;M. Lu;M. Reth-M.-R
通讯作者：
K. Laugwitz;A. Moretti;J. Lam;P. Gruber;Y. Chen;S. Woodard;L. Lin;C. Cai;M. Lu;M. Reth-M.-R
影响因子：
11.4
作者：
Hecht, A;Vleminckx, K;Kemler, R
通讯作者：
Kemler, R
DOI：
10.1073/pnas.0704044104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Kwon, Chulan;Arnold, Joshua;Srivastava, Deepak
通讯作者：
Srivastava, Deepak