Distribution of histone3 lysine 4 trimethylation at T3-responsive loci in the heart during reversible changes in gene expression.
Distribution of histone3 lysine 4 trimethylation at T3-responsive loci in the heart during reversible changes in gene expression.
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DOI：
10.3727/105221612x13372578119698
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Smithies O
中科院分区：
文献类型：
--
作者：
Pandya K;Kohro T;Mimura I;Kobayashi M;Wada Y;Kodama T;Smithies O
成人心脏中许多心脏基因的表达，包括构成心脏肌球蛋白重链位点 (Myh) 的两个基因，受甲状腺激素 (T3) 水平控制，但当这些基因的表达发生变化时，有关这些基因的表观遗传状态的信息很少。我们给小鼠喂食正常食物或丙硫尿嘧啶（PTU，T3 生成抑制剂）饮食 6 周，或喂食 PTU 饮食 6 周，然后再喂食正常食物两周。然后将这些组的心室用于使用 H3K4me3 抗体进行 ChIP-seq 分析，H3K4me3 是一种有据可查的基因激活表观遗传标记。结果数据表明，在 Myh7 基因座，H3K4me3 修饰主要在 5' 转录区被诱导，同时 β 肌球蛋白重链 (MHC) 表达增加。在 Myh6 位点，H3K4me3 修饰的减少发生在启动子和 5' 转录区域。广泛的 H3K4me3 修饰也发生在两个 Myh 基因之间的基因间区域，该区域延伸到 Myh7 的 3' 转录区域。 PTU 引起的 H3K4me3 水平变化大部分是可逆的，但并不总是完全的。我们发现在 PTU 撤除后 Myh6 基因表达完全恢复，然而 H3K4me3 模式仅在 Myh6 上部分恢复，这表明 Myh6 的完全重新表达不需要 H3K4me3 修饰完全恢复到未处理条件。总之，我们的数据表明 H3K4me3 修饰是与 Myh 基因表达变化密切相关的表观遗传标记。
Expression in the adult heart of a number of cardiac genes, including the two genes comprising the cardiac Myosin heavy chain locus (Myh), is controlled by thyroid hormone (T3) levels, but there is minimal information concerning the epigenetic status of the genes when their expressions change. We fed mice normal chow or a Propyl thio uracil (PTU, an inhibitor of T3 production)-diet for 6 weeks, or the PTU diet for 6 weeks followed by normal chow for a further two weeks. Heart ventricles from these groups were then used for ChIP-seq analyses with an antibody to H3K4me3, a well documented epigenetic marker of gene activation. The resulting data show that, at the Myh7 locus, H3K4me3 modifications are induced primarily at 5’ transcribed region in parallel with increased expression of beta myosin heavy chain (MHC). At the Myh6 locus, decreases in H3K4me3 modifications occurred at the promoter and 5’ transcribed region. Extensive H3K4me3 modifications also occurred at the intergenic region between the two Myh genes which extended into the 3’ transcribed region of Myh7. The PTU-induced changes in H3K4me3 levels are, for the most part, reversible but are not invariably complete. We found full restoration of Myh6 gene expression upon PTU withdrawal, however the H3K4me3 pattern was only partially restored at Myh6, suggesting that full re-expression of Myh6 does not require that the H3K4me3 modifications return fully to the untreated conditions. Together, our data show that the H3K4me3 modification is an epigenetic marker closely associated with changes in Myh gene expression.
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DOI：
10.1126/science.1162253
发表时间：
2008-12-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Seila AC;Calabrese JM;Levine SS;Yeo GW;Rahl PB;Flynn RA;Young RA;Sharp PA
通讯作者：
Sharp PA
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
16
作者：
Ishihara, Ko;Oshimura, Mitsuo;Nakao, Mitsuyoshi
通讯作者：
Nakao, Mitsuyoshi
影响因子：
64.8
作者：
Santos-Rosa, H;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
DOI：
10.1152/ajpheart.01111.2005
发表时间：
2006-06-01
影响因子：
4.8
作者：
Haddad, F;Qin, AX;Baldwin, KM
通讯作者：
Baldwin, KM