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首页> 外文期刊>Journal of Cellular Physiology >Dynamic Histone Acetylation of H3K4me3 Nucleosome Regulates MCL1 Pre-mRNA Splicing
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Dynamic Histone Acetylation of H3K4me3 Nucleosome Regulates MCL1 Pre-mRNA Splicing

机译：动态的组蛋白乙酰化作用H3K4me3核小体调节MCL1 Pre-mRNA拼接

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摘要

Pre-mRNA splicing is a cotranscriptional process affected by the chromatin architecture along the body of coding genes. Recruited to the pre-mRNA by splicing factors, histone deacetylases (HDACs) and K-acetyltransferases (KATs) catalyze dynamic histone acetylation along the gene. In colon carcinoma HCT 116 cells, HDAC inhibition specifically increased KAT2B occupancy as well as H3 and H4 acetylation of the H3K4 trimethylated (H3K4me3) nucleosome positioned over alternative exon 2 of the MCL1 gene, an event paralleled with the exclusion of exon 2. These results were reproduced in MDA-MB-231, but not in MCF7 breast adenocarcinoma cells. These later cells have much higher levels of demethylase KDM5B than either HCT 116 or MDA-MB-231 cells. We show that H3K4me3 steady-state levels and H3K4me3 occupancy at the end of exon 1 and over exon 2 of the MCL1 gene were lower in MCF7 than in MDA-MB-231 cells. Furthermore, in MCF7 cells, there was minimal effect of HDAC inhibition on H3/H4 acetylation and H3K4me3 levels along the MCL1 gene and no change in pre-mRNA splicing choice. These results show that, upon HDAC inhibition, the H3K4me3 mark plays a critical role in the exclusion of exon 2 from the MCL1 pre-mRNA. J. Cell. Physiol. 231: 2196-2204, 2016. (c) 2016 Wiley Periodicals, Inc.
机译：Pre-mRNA拼接是一个cotranscriptional过程影响染色质结构沿身体的编码基因。通过拼接因素,组蛋白去乙酰酶抑制剂(hdac)和K-acetyltransferases (kat)催化活力组蛋白乙酰化作用的基因。116细胞癌HCT, HDAC抑制特别是KAT2B入住率以及增加H3和H4的乙酰化H3K4 trimethylated(H3K4me3)核小体定位的选择MCL1的第2外显子基因,平行于一个事件外显子2的排斥。在mda - mb - 231复制,但不是在MCF7乳房腺癌的细胞。更高水平的demethylase KDM5B比HCT 116或mda - mb - 231细胞。稳态和H3K4me3入住率水平外显子1月底MCL1基因外显子2的比在低MCF7 mda - mb - 231细胞。此外,在MCF7细胞,有最小HDAC抑制对H3和H4乙酰化作用的影响沿着MCL1和H3K4me3水平基因也没有改变pre-mRNA拼接的选择。表明,HDAC抑制,H3K4me3标志中起关键作用的外显子2的排斥从MCL1 pre-mRNA。2196 - 2204年,2016年。

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