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CBP/p300 和 SIRT1 参与 S 期特异性组蛋白基因的转录调控。

CBP/p300 and SIRT1 are involved in transcriptional regulation of S-phase specific histone genes.

机构信息

Institute of Molecular and Cell Biology, Singapore, Singapore.

出版信息

PLoS One. 2011;6(7):e22088. doi: 10.1371/journal.pone.0022088. Epub 2011 Jul 15.

DOI:10.1371/journal.pone.0022088
PMID:21789216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3137613/
Abstract

BACKGROUND

Histones constitute a type of essential nuclear proteins important for chromatin structure and functions. The expression of major histones is strictly confined to the S phase of a cell cycle and tightly coupled to DNA replication.

METHODOLOGY/PRINCIPAL FINDINGS: With RT-qPCR and ChIP assays, we investigated transcriptional regulation of the S-phase specific histone genes and found that the acetylation level of histones on core histone gene promoters fluctuated during cell cycle in a pattern similar to RNA polymerase II association. Further, we showed that CBP/p300 and SIRT1 were recruited to histone gene promoters in an NPAT-dependent manner, knockdown of which affected histone acetylation on histone gene promoters and histone gene transcription.

SIGNIFICANCE

These observations contribute to further understanding of the mechanism by which the expression of canonical histone genes is regulated, and also implicate a link between histone expression and DNA damage repair and cell metabolism.

摘要

背景

组蛋白是构成核蛋白的重要类型，对于染色质结构和功能至关重要。主要组蛋白的表达严格局限于细胞周期的 S 期，并与 DNA 复制紧密偶联。

方法/主要发现：通过 RT-qPCR 和 ChIP 分析，我们研究了 S 期特异性组蛋白基因的转录调控，发现组蛋白在核心组蛋白基因启动子上的乙酰化水平在细胞周期中呈波动变化，与 RNA 聚合酶 II 结合的模式相似。此外，我们表明 CBP/p300 和 SIRT1 以 NPAT 依赖性的方式被招募到组蛋白基因启动子上，其敲低会影响组蛋白基因启动子上的组蛋白乙酰化和组蛋白基因转录。

意义

这些观察结果有助于进一步了解经典组蛋白基因表达调控的机制，并暗示组蛋白表达与 DNA 损伤修复和细胞代谢之间存在联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/54405ac9ea67/pone.0022088.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/d7a389848b59/pone.0022088.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/7b4a070d7abe/pone.0022088.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/6a853873082f/pone.0022088.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/35cedd8d9bdd/pone.0022088.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/43245c3dcfef/pone.0022088.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/115e9bf12f06/pone.0022088.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/44d4a69c4809/pone.0022088.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/94a450ce4c3a/pone.0022088.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/2c80344bb5b6/pone.0022088.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/54405ac9ea67/pone.0022088.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/d7a389848b59/pone.0022088.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/7b4a070d7abe/pone.0022088.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/6a853873082f/pone.0022088.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/35cedd8d9bdd/pone.0022088.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/43245c3dcfef/pone.0022088.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/115e9bf12f06/pone.0022088.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/44d4a69c4809/pone.0022088.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/94a450ce4c3a/pone.0022088.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/2c80344bb5b6/pone.0022088.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bc/3137613/54405ac9ea67/pone.0022088.g010.jpg

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