Acute Stress Enhances Epigenetic Modifications But Does Not Affect the Constitutive Binding of pCREB to Immediate-Early Gene Promoters in the Rat Hippocampus.
Acute Stress Enhances Epigenetic Modifications But Does Not Affect the Constitutive Binding of pCREB to Immediate-Early Gene Promoters in the Rat Hippocampus.
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DOI：
10.3389/fnmol.2017.00416
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发表时间：
2017
影响因子：
4.8
通讯作者：
Reul JMHM
中科院分区：
文献类型：
--
作者：
Carter SD;Mifsud KR;Reul JMHM
即刻早期基因(IEGs)c-Fos和Egr-1在暴露于急性应激源后，在海马区稀疏的神经元中迅速而瞬时地被诱导。这些基因的诱导是成功的行为适应压力的分子机制的关键部分。我们以前的工作表明，c-Fos和Egr-1在海马区的转录激活需要在其启动子区域形成双组蛋白标记，组蛋白H3的丝氨酸10的磷酸化和组蛋白H3的赖氨酸9/14的乙酰化。在本研究中，我们利用染色质免疫沉淀法(ChIP)发现，在活体内FS应激后，c-Fos和Egr-1启动子内H3K9ac-S10p的形成增加，并且这些组蛋白修饰位于含有cAMP反应元件(Cres)的启动子区域，而不是仅含有血清反应元件(SRE)的邻近区域。然而，令人惊讶的是，随后的芯片分析显示，FS后pCREB或CREB结合蛋白(CBP)与Cres的结合没有变化。事实上，pCREB与c-Fos和Egr-1启动子的结合在基线条件下已经高度丰富，在胁迫后不会进一步增加。我们认为，结构性的pCREB结合可能使c-Fos和Egr-1处于激活的稳定状态。H3K9ac-S10p在Cre位点附近的形成可能通过招募额外的表观遗传因子参与解锁转录延伸。
The immediate early genes (IEGs) c-Fos and Egr-1 are rapidly and transiently induced in sparse neurons within the hippocampus after exposure to an acute stressor. The induction of these genes is a critical part of the molecular mechanisms underlying successful behavioral adaptation to stress. Our previous work has shown that transcriptional activation of c-Fos and Egr-1 in the hippocampus requires formation of a dual histone mark within their promoter regions, the phosphorylation of serine 10 and acetylation of lysine 9/14 of histone H3. In the present study, using chromatin immuno-precipitation (ChIP), we found that an increase in the formation of H3K9ac-S10p occurs within the c-Fos and Egr-1 promoters after FS stress in vivo and that these histone modifications were located to promoter regions containing cAMP Responsive Elements (CREs), but not in neighboring regions containing only Serum Responsive Elements (SREs). Surprisingly, however, subsequent ChIP analyses showed no changes in the binding of pCREB or CREB-binding protein (CBP) to the CREs after FS. In fact, pCREB binding to the c-Fos and Egr-1 promoters was already highly enriched under baseline conditions and did not increase further after stress. We suggest that constitutive pCREB binding may keep c-Fos and Egr-1 in a poised state for activation. Possibly, the formation of H3K9ac-S10p in the vicinity of CRE sites may participate in unblocking transcriptional elongation through recruitment of additional epigenetic factors.
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影响因子：
4.7
作者：
Chandramohan, Yalini;Droste, Susanne K.;Reul, Johannes M. H. M.
通讯作者：
Reul, Johannes M. H. M.
影响因子：
3
作者：
Carter SD;Mifsud KR;Reul JM
通讯作者：
Reul JM
影响因子：
64.5
作者：
BOURTCHULADZE, R;FRENGUELLI, B;SILVA, AJ
通讯作者：
SILVA, AJ
影响因子：
2.9
作者：
Bullock, BP;Habener, JF
通讯作者：
Habener, JF
影响因子：
3.4
作者：
Bilang-Bleuel, A;Ulbricht, S;Reul, JMHM
通讯作者：
Reul, JMHM