Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo.
Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo.
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不同的表观遗传学计划调节体内人心脏中心肌细胞的发育和疾病。
DOI：
10.1038/s41467-017-02762-z
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发表时间：
2018-01-26
影响因子：
16.6
通讯作者：
Hein L
中科院分区：
文献类型：
--
作者：
Gilsbach R;Schwaderer M;Preissl S;Grüning BA;Kranzhöfer D;Schneider P;Nührenberg TG;Mulero-Navarro S;Weichenhan D;Braun C;Dreßen M;Jacobs AR;Lahm H;Doenst T;Backofen R;Krane M;Gelb BD;Hein L
心肌细胞分化所必需的表观遗传机制和转录因子网络已被揭示。然而，在胎儿发育、出生后成熟和疾病中，这些终末分化细胞的表观基因组的重塑仍然未知。在这里，我们调查动态的心肌细胞表观基因组在发展过程中和慢性心力衰竭。我们发现，产前发育和出生后成熟的特点是积极的CpG甲基化和组蛋白标记的合作，在顺式调节和基因区域，塑造心肌细胞转录组。相反，终末期心力衰竭的病理性基因表达伴随着活性组蛋白标记的变化，而没有CpG甲基化和抑制性染色质标记的重大改变。值得注意的是，心肌细胞中的顺式调节区显著富集心血管疾病相关变体。这项研究揭示了不同层次的表观遗传调控不仅在产前发育和出生后的成熟，而且在患病的人心肌细胞。心肌细胞表观基因组在发育、出生后成熟和疾病过程中是如何重排的还不清楚。在这里，作者研究了人类心肌细胞表观基因组在发展和慢性心力衰竭，并确定不同的表观遗传程序调节这些过程。
Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation, and in disease remains unknown. Here, we investigate the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. We find that prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome. In contrast, pathological gene expression in terminal heart failure is accompanied by changes in active histone marks without major alterations in CpG methylation and repressive chromatin marks. Notably, cis-regulatory regions in cardiac myocytes are significantly enriched for cardiovascular disease-associated variants. This study uncovers distinct layers of epigenetic regulation not only during prenatal development and postnatal maturation but also in diseased human cardiac myocytes. How the cardiac myocyte epigenome is rearranged during development, postnatal maturation and disease is not well understood. Here, the authors investigate the human cardiac myocyte epigenome during development and chronic heart failure and identify distinct epigenetic programs regulating these processes.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1073/pnas.1016959108
发表时间：
2011-04-05
影响因子：
11.1
作者：
He, Aibin;Kong, Sek Won;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
14.9
作者：
Burger L;Gaidatzis D;Schübeler D;Stadler MB
通讯作者：
Stadler MB
影响因子：
64.5
作者：
Anand P;Brown JD;Lin CY;Qi J;Zhang R;Artero PC;Alaiti MA;Bullard J;Alazem K;Margulies KB;Cappola TP;Lemieux M;Plutzky J;Bradner JE;Haldar SM
通讯作者：
Haldar SM
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.