The BCL2 gene is regulated by a special AT-rich sequence binding protein 1-mediated long range chromosomal interaction between the promoter and the distal element located within the 3'-UTR.
The BCL2 gene is regulated by a special AT-rich sequence binding protein 1-mediated long range chromosomal interaction between the promoter and the distal element located within the 3'-UTR.
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DOI：
10.1093/nar/gkr023
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发表时间：
2011-06
影响因子：
14.9
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Gong F;Sun L;Wang Z;Shi J;Li W;Wang S;Han X;Sun Y
BCL 2基因3′-非翻译区（3′-UTR）内的279 bp的主要断裂点区域（mbr）是富含AT序列结合蛋白1（SATB 1）的结合位点，SATB 1参与基因转录的远程调控。我们前期的研究表明mbr可以在200-kb的距离内调控BCL 2的转录，并且这种调控功能与SATB 1密切相关。本研究旨在探讨其机制及其与细胞凋亡的关系。通过染色体构象捕获（3C）和染色质免疫沉淀（ChIP）分析，我们证明了mbr可以通过SATB 1介导的染色质成环与BCL 2启动子物理相互作用，这是启动子的表观遗传修饰、CREB可及性和BCL 2基因的高表达所必需的。在细胞凋亡早期，SATB 1是BCL 2表达的关键调节因子。通过用半胱天冬酶-6抑制剂处理细胞或过表达对半胱天冬酶-6具有抗性的突变体SATB 1来抑制SATB 1切割，抑制SATB 1介导的染色质环的分解并恢复Jurkat细胞中的BCL 2 mRNA水平。这些数据揭示了BCL 2调节的新机制，并首次将SATB 1介导的长程相互作用与控制细胞凋亡途径的基因的调节机制联系起来。
The 279-bp major breakpoint region (mbr) within the 3′-untranslated region (3′-UTR) of the BCL2 gene is a binding site of special AT-rich sequence binding protein 1 (SATB1) that is well known to participate in the long-range regulation of gene transcription. Our previous studies have revealed that the mbr could regulate BCL2 transcription over a 200-kb distance and this regulatory function was closely related to SATB1. This study is to explore the underlying mechanism and its relevance to cellular apoptosis. With chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP) assays we demonstrated that the mbr could physically interact with BCL2 promoter through SATB1-mediated chromatin looping, which was required for epigenetic modifications of the promoter, CREB accessibility and high expression of the BCL2 gene. During early apoptosis, SATB1 was a key regulator of BCL2 expression. Inhibition of SATB1 cleavage by treatment of cells with a caspase-6 inhibitor or overexpression of mutant SATB1 that was resistant to caspase-6, inhibited disassembly of the SATB1-mediated chromatin loop and restored the BCL2 mRNA level in Jurkat cells. These data revealed a novel mechanism of BCL2 regulation and mechanistically link SATB1-mediated long-range interaction with the regulation of a gene controlling apoptosis pathway for the first time.
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影响因子：
2.6
作者：
Fujii, Y;Kumatori, A;Nakamura, M
通讯作者：
Nakamura, M
影响因子：
64.5
作者：
DICKINSON, LA;JOH, T;KOHWISHIGEMATSU, T
通讯作者：
KOHWISHIGEMATSU, T
影响因子：
5.4
作者：
Kumar, Pavan P.;Mehta, Sameet;Galande, Sanjeev
通讯作者：
Galande, Sanjeev
DOI：
10.4049/jimmunol.0901781
发表时间：
2009-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liu Z;Ma Z;Terada LS;Garrard WT
通讯作者：
Garrard WT
DOI：
10.1101/sqb.1999.64.351
发表时间：
1999-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Adams, JM;Huang, DCS;Cory, S
通讯作者：
Cory, S