Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice.
Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice.
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DOI：
10.1186/s12864-018-4752-4
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发表时间：
2018-05-10
期刊：
影响因子：
4.4
通讯作者：
Makino S
中科院分区：
文献类型：
--
作者：
Oda M;Wakabayashi S;Ari Wijetunga N;Yuasa S;Enomoto H;Kaneda R;Yoon SH;Mittal N;Jing Q;Suzuki M;Greally JM;Fukuda K;Makino S
细胞类型特异性基因在基因组环境中表现出异质性，并且取决于所涉及的细胞类型，可能通过不同的基因转录过程受到不同的表观遗传调控。一些心肌细胞（CM）特异性基因的基因体区（GBR）在CM中是长的和高度低甲基化的。为了探索表观遗传模式和功能的细胞类型特异性，在CM、肝细胞和胚胎干细胞（ESC）之间比较GBR的多种表观遗传修饰。我们发现，大多数基因的转录水平和基因长度之间呈中度负相关。由于CM特异性基因通常比其他细胞类型特异性基因长，我们假设CM的基因体表观遗传特征可能支持CM特异性基因的转录调控。我们发现基因体DNA低甲基化在CM特异性基因亚群共定位与罕见的基因体标记，包括RNA聚合酶II（Pol II）和p300。有趣的是，5-羟甲基胞嘧啶（5 hmC）内的基因体内标记细胞类型特异性基因在新生儿阶段和活跃的基因体组蛋白标记H3 K36三甲基化下降，并与细胞类型特异性基因体DNA低甲基化和选择性Pol II/p300积累在成年期重叠。还观察到基因体表观遗传修饰的不同组合与全基因组规模的细胞类型特异性，揭示了不同细胞类型GBR中动态表观遗传重排的发生。由于5 hmC富集进行到低甲基化GBR，我们认为低甲基化可能不代表静态，而是由于与转录相关的局部甲基化和导致去甲基化的泰特氧化修饰之间的平衡而代表周转的平衡状态。因此，我们得出结论，CM中的去甲基化可以用于建立与肝细胞相关的这种细胞类型特异性表观遗传结构域。细胞类型特异性表观遗传控制的建立也可能改变进化的基因组背景，并可能有助于细胞类型特异性转录协调的发展。本文的在线版本（10.1186/s12864-018-4752-4）包含补充材料，可供授权用户使用。
Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs). We found that most genes show a moderately negative correlation between transcript levels and gene lengths. As CM-specific genes are generally longer than other cell-type-specific genes, we hypothesized that the gene-body epigenetic features of CMs may support the transcriptional regulation of CM-specific genes. We found gene-body DNA hypomethylation in a CM-specific gene subset co-localized with rare gene-body marks, including RNA polymerase II (Pol II) and p300. Interestingly, 5-hydroxymethylcytosine (5hmC) within the gene body marked cell-type-specific genes at neonatal stages and active gene-body histone mark H3K36 trimethylation declined and overlapped with cell-type-specific gene-body DNA hypomethylation and selective Pol II/p300 accumulation in adulthood. Different combinations of gene-body epigenetic modifications were also observed with genome-wide scale cell-type specificity, revealing the occurrence of dynamic epigenetic rearrangements in GBRs across different cell types. As 5hmC enrichment proceeded to hypomethylated GBRs, we considered that hypomethylation may not represent a static state but rather an equilibrium state of turnover due to the balance between local methylation linked to transcription and Tet oxidative modification causing demethylation. Accordingly, we conclude that demethylation in CMs can be a used to establish such cell-type-specific epigenetic domains in relation to liver cells. The establishment of cell-type-specific epigenetic control may also change genomic contexts of evolution and may contribute to the development of cell-type-specific transcriptional coordination. The online version of this article (10.1186/s12864-018-4752-4) contains supplementary material, which is available to authorized users.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
3.7
作者：
Diehl F;Brown MA;van Amerongen MJ;Novoyatleva T;Wietelmann A;Harriss J;Ferrazzi F;Böttger T;Harvey RP;Tucker PW;Engel FB
通讯作者：
Engel FB
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
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
心脏成纤维细胞通过Beta1整合素信号传导调节心肌增殖。
影响因子：
11.8
作者：
Leda, Masaki;Tsuchihashi, Takatoshi;Ivey, Kathryn N.;Ross, Robert S.;Hong, Ting-Ting;Shaw, Robin M.;Srivastava, Deepak
通讯作者：
Srivastava, Deepak