Activation of terminal B cell differentiation by inhibition of histone deacetylation
Activation of terminal B cell differentiation by inhibition of histone deacetylation
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DOI：
10.1016/s0161-5890(03)00029-4
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发表时间：
2003-05-01
影响因子：
3.6
通讯作者：
Insel, RA
中科院分区：
文献类型：
--
作者：
Lee, SC;Bottaro, A;Insel, RA
在成熟B淋巴瘤L10 A和小鼠脾B细胞中研究了组蛋白乙酰化在调节终末B细胞分化中的作用，组蛋白乙酰化可以改变DNA对转录调节蛋白的可接近性并有助于基因表达。L10 A细胞与组蛋白去乙酰化酶（HDAC）抑制剂阿司他丁A（TSA）和丁酸盐孵育增加Blimp-1、J链和mad基因的表达，降低c-myc和BSAP/Pax-5基因的表达，增加表面CD 43和Syndecan-1的表达，并降低表面IgM。脾B细胞与TSA和葡聚糖缀合的抗IgD Ab孵育增加Blimp-1基因和Syndecan-1表面表达。基因表达和细胞表面标志物的改变与诱导终末B细胞分化的发生一致。L10 A细胞与TSA和放线菌酮（CHX）共孵育废除了Blimp-1表达的上调，表明TSA激活的Blimp-1表达需要转录激活因子的合成。与此相反，在与TSA和放线菌酮或放线菌酮单独培养的L10 A细胞中，mad表达增加，这表明mad表达可能独立于Blimp-1表达而发生，并且受不稳定的HDAC相关转录抑制因子的调节。结果表明，组蛋白乙酰化调节基因的转录控制终端B细胞分化。(C)2003爱思唯尔科技有限公司版权所有。
A role for histone acetylation, which can alter the accessibility of DNA to transcriptional regulatory proteins and contribute to gene expression, in regulating terminal B cell differentiation was investigated in the mature B lymphoma L10A and mouse splenic B cells. Incubation of the L10A cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and butyrate increased expression of Blimp-1, J chain, and mad genes, decreased expression of c-myc and BSAP/Pax-5 genes, increased the expression of surface CD43 and Syndecan-1, and decreased surface IgM. Incubation of splenic B cells with TSA and dextran conjugated anti-IgD Ab increased Blimp-1 gene and Syndecan-1 surface expression. The alteration in gene expression and cell surface markers was consistent with induction of the onset of terminal B cell differentiation. Co-incubation of L10A cells with TSA and cycloheximide (CHX) abrogated the up-regulation of Blimp-1 expression, indicating that TSA-activated Blimp-1 expression required synthesis of a transcriptional activator. In contrast, mad expression was increased in L10A cells cultured with TSA and cycloheximide or cycloheximide alone, suggesting mad expression may occur independent of Blimp-1 expression and is regulated by a labile, HDAC associated transcriptional repressor. The results demonstrate that histone acetylation regulates transcription of genes controlling terminal B cell differentiation. (C) 2003 Elsevier Science Ltd. All rights reserved.