Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells
Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells
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DOI：
10.1006/bbrc.1997.8033
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发表时间：
1998-01-26
影响因子：
3.1
通讯作者：
Gullans, SR
中科院分区：
文献类型：
--
作者：
Dangond, F;Hafler, DA;Gullans, SR
核小体组蛋白可以通过组蛋白乙酰转移酶(HATS)和脱乙酰基酶(HDACs)的可逆乙酰化修饰。HATS诱导核小体松弛，并允许转录激活剂与DNA结合。HDAC形成辅阻遏物复合体，负向调节细胞生长。然而，HDAC抑制剂丁酸盐和曲古抑素A阻断了T细胞的增殖，这表明HDAC并不是所有的作用都会导致抑制。利用mRNA差异显示和5‘RACE技术，我们分离到人HDAC3基因，这是一个在PHA激活的T细胞克隆中上调的新基因。HDAC3与其他人类HDACs和酵母RPD3同源。在外周血单核细胞(PBMC)中，PHA、PMA和α-CD3的激活可增加HDAC mRNA的表达，但对干扰素-γ、脂多糖或IL-4无明显影响。相反，GMCSF下调外周血单核细胞HDAC3mRNA水平。免疫组织和非免疫组织中均有HDAC的广泛表达。在人髓系白血病THP-1细胞中，HDAC3基因可导致细胞体积增大、核形态异常和细胞周期G2/M期聚集。组蛋白脱乙酰酶实验证实表达的HDAC3蛋白在α-HDAC3抗体免疫沉淀物中具有功能活性。我们的研究提示HDACs参与了细胞周期的进程和激活。(C)1998年学术出版社。
The nucleosomal histones can be modified through reversible acetylation by histone acetyltransferases (HATs) and deacetylases (HDACs). HATs induce nucleosomal relaxation and allow DNA-binding by transcriptional activators. HDACs form corepressor complexes which negatively regulate cell growth. However, the HDAC inhibitors butyrate and Trichostatin A block T cell proliferation, suggesting that not all effects of HDACs lead to repression. Using mRNA differential display and 5'RACE we isolated human HDAC3, a novel gene that is upregulated in PHA-activated T cell clones. HDAC3 is homologous to other human HDACs and yeast RPD3. In peripheral blood mononuclear cells (PBMCs), activation by PHA, PMA and alpha-CD3 increased HDAC mRNA but no effect was seen with IFN-gamma, LPS, or IL-4. In contrast, GMCSF downregulated PBMC levels of HDAC3 mRNA. All HDACs were found to be ubiquitously expressed in immune and non-immune tissues. In human myeloid leukemia THP-1 cells, HDAC3 transfection resulted in increased size, aberrant nuclear morphology and cell cycle G2/M cell accumulation. Functional activity of the expressed HDAC3 protein was confirmed in alpha-HDAC3 antibody immunoprecipitates by a histone deacetylase assay. Our study suggests the participation of HDACs in cell cycle progression and activation. (C) 1998 Academic Press.