Ontogenic expression of hepatic Ahr mRNA is associated with histone H3K4 di-methylation during mouse liver development
Ontogenic expression of hepatic Ahr mRNA is associated with histone H3K4 di-methylation during mouse liver development
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DOI：
10.1016/j.toxlet.2009.05.017
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发表时间：
2009-09-28
影响因子：
3.5
通讯作者：
Klaassen, Curtis D.
中科院分区：
文献类型：
--
作者：
Cui, Yue Julia;Yeager, Ronnie L.;Klaassen, Curtis D.
芳香烃受体（Ahr）是一种异生物质传感器，调节一系列药物代谢基因的表达。然而，Ahr对正常的肝脏发育也很重要。本研究的目的是研究小鼠肝脏Ahr mRNA的个体发生，并确定在出生后肝脏发育过程中调控Ahr基因转录的表观遗传机制。出生前2天至出生后45天，肝脏Ahr mRNA增加了224%。ChIP芯片分析表明，DNA甲基化和组蛋白H3K27三甲基化（H3K27Me3），基因转录抑制的两个表观遗传标记，在Ahr基因位点周围始终较低。与此相反，富集组蛋白H3K4二甲基化（H3K4Me2），基因激活的标志，增加了182%，从产前到年轻的成年人时期周围的Ahr基因位点。回归分析显示，H3K4Me2和Ahr mRNA的富集之间的强相关性（r = 0.91）。总之，出生后H3K4Me2富集与Ahr mRNA在发育中的小鼠肝脏中正相关，提供允许Ahr基因在出生后肝脏发育中反式激活的容许染色质状态。出版社：Elsevier爱尔兰Ltd.
The aryl hydrocarbon receptor (Ahr) is a xenobiotic sensor that regulates the expression of a battery of drug-metabolizing genes. However, Ahr is also important for normal liver development. The purpose of the present study was to examine the ontogeny of Ahr mRNA in mouse liver, and determine the epigenetic mechanisms regulating Ahr gene transcription during postnatal liver development. There was a 224% increase in hepatic Ahr mRNA from 2 days before birth to 45 days after birth. ChIP-on-chip analysis demonstrated that DNA methylation and histone H3K27 tri-methylation (H3K27Me3), two epigenetic marks for suppression of gene transcription, were consistently low around the Ahr gene locus. In contrast, enrichment of histone H3K4 di-methylation (H3K4Me2), a hallmark for gene activation, increased 182% from prenatal to young adult period around the Ahr gene locus. Regression analysis revealed a strong correlation between enrichment of H3K4Me2 and Ahr mRNA (r = 0.91). In conclusion, postnatal H3K4Me2 enrichment positively associates with Ahr mRNA in developing mouse liver, providing a permissive chromatin state allowing Ahr gene transactivation in postnatal liver development. Published by Elsevier Ireland Ltd.