Epigenetics of Mitochondria-Associated Genes in Striated Muscle.
Epigenetics of Mitochondria-Associated Genes in Striated Muscle.
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DOI：
10.3390/epigenomes6010001
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发表时间：
2021-12-22
期刊：
影响因子：
2.5
通讯作者：
Ehrlich M
中科院分区：
文献类型：
--
作者：
Ehrlich KC;Deng HW;Ehrlich M
横纹肌有特别大的能量需求。我们鉴定了97个基因优先在骨骼肌和心脏中表达，而在主动脉中不表达，并发现它们之间的线粒体相关性显著富集。我们比较了与横纹肌和线粒体相关的27个基因的表观基因组学和转录组学特征。许多显示出它们的组织特异性转录水平之间的强相关性，和它们的组织特异性启动子，增强子，或开放染色质，以及它们的DNA低甲基化。他们的横纹肌特异性增强子染色质位于基因的内部、上游或下游，作为超级增强子（CKMT 2、SLC 25 A4和ACO 2）贯穿基因的大部分，甚至与相邻基因（COX 6A 2、COX 7A 1和COQ 10A）重叠。令人惊讶的是，1.38 Mb PRKN（PARK 2）基因（参与线粒体自噬并与青少年帕金森病相关）的3′端显示骨骼肌/成肌细胞特异性增强子染色质，成肌细胞特异性反义RNA，以及脑特异性增强子染色质。我们还在脑和胚胎干细胞中发现了PPARGC 1A（PGC-1α）内的新型组织特异性RNA，该RNA编码线粒体形成和代谢的主转录辅助调节因子。该基因的四个替代启动子（包括肌肉相关启动子）的组织特异性与附近的增强子染色质和开放染色质相关。我们对这些基因进行了深入的表观遗传学检查，发现了以前未描述的组织特异性增强子染色质、基因内启动子、DNA低甲基化区域和基因内非编码RNA，这些基因为这组医学上重要的基因的转录控制提供了新的见解。
Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated with striated muscle and mitochondria. Many showed strong correlations between their tissue-specific transcription levels, and their tissue-specific promoter, enhancer, or open chromatin as well as their DNA hypomethylation. Their striated muscle-specific enhancer chromatin was inside, upstream, or downstream of the gene, throughout much of the gene as a super-enhancer (CKMT2, SLC25A4, and ACO2), or even overlapping a neighboring gene (COX6A2, COX7A1, and COQ10A). Surprisingly, the 3′ end of the 1.38 Mb PRKN (PARK2) gene (involved in mitophagy and linked to juvenile Parkinson’s disease) displayed skeletal muscle/myoblast-specific enhancer chromatin, a myoblast-specific antisense RNA, as well as brain-specific enhancer chromatin. We also found novel tissue-specific RNAs in brain and embryonic stem cells within PPARGC1A (PGC-1α), which encodes a master transcriptional coregulator for mitochondrial formation and metabolism. The tissue specificity of this gene’s four alternative promoters, including a muscle-associated promoter, correlated with nearby enhancer chromatin and open chromatin. Our in-depth epigenetic examination of these genes revealed previously undescribed tissue-specific enhancer chromatin, intragenic promoters, regions of DNA hypomethylation, and intragenic noncoding RNAs that give new insights into transcription control for this medically important set of genes.
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影响因子：
5.5
作者：
Gouspillou, Gilles;Godin, Richard;Hussain, Sabah N. A.
通讯作者：
Hussain, Sabah N. A.
影响因子：
14.9
作者：
Khan A;Zhang X
通讯作者：
Zhang X
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
14.9
作者：
Haeussler M;Zweig AS;Tyner C;Speir ML;Rosenbloom KR;Raney BJ;Lee CM;Lee BT;Hinrichs AS;Gonzalez JN;Gibson D;Diekhans M;Clawson H;Casper J;Barber GP;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ
影响因子：
64.5
作者：
Bergmann, Olaf;Zdunek, Sofia;Frisen, Jonas
通讯作者：
Frisen, Jonas