Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A.
Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A.
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DOI：
10.1016/j.bbagrm.2018.03.002
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Abdellatif M
中科院分区：
文献类型：
--
作者：
Shin H;He M;Yang Z;Jeon YH;Pfleger J;Sayed D;Abdellatif M
调节H2A.Z及其在分化的哺乳动物细胞中转录的需要的机制仍然不明确。在本研究中，我们在酵母双杂交筛选中鉴定了ANP 32 e的C-末端和H2 A. Z的N-末端之间的相互作用。敲低ANP 32 e导致蛋白酶体降解和H2 A. Z或融合至其N-末端的嵌合绿色荧光蛋白的核耗竭。这种效果被逆转蛋白磷酸酶2A（PP 2A）的抑制，相反，其催化亚基的过度表达再现。因此，敲低ANP 32 e抑制H2A.Z的磷酸化，而丝氨酸-9的突变证明了其对蛋白质稳定性和核定位的需要，敲低核有丝分裂原和应激诱导激酶1也是如此。此外，ANP 32 e的敲除还揭示了其对细胞信号传导和基因表达的差异需求，而全基因组结合分析证实了其与H2A.Z在转录起始位点以及诱导型和组织特异性基因的基因体的共定位。数据还表明，H2A.Z限制转录，这是由ANP 32 e在启动子和表达基因的基因体调节。因此，ANP 32 e通过抑制PP 2A，是核小体包含H2A.Z和基因表达调控所必需的。
The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit. Accordingly, knockdown of ANP32e inhibited phosphorylation of H2A.Z, whereas a mutation of serine-9 proved its requirement for both the protein’s stability and nuclear localization, as did knockdown of the nuclear mitogen and stress-induced kinase 1. Moreover, ANP32e’s knockdown also revealed its differential requirement for cell signaling and gene expression, whereas, genome-wide binding analysis confirmed its co-localization with H2A.Z at transcription start sites, as well as, gene bodies of inducible and tissue-specific genes. The data also suggest that H2A.Z restricts transcription, which is moderated by ANP32e at the promoter and gene bodies of expressed genes. Thus, ANP32e, through inhibition of PP2A, is required for nucleosomal inclusion of H2A.Z and the regulation of gene expression.
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DOI：
10.1093/bioinformatics/btp472
发表时间：
2009-10-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Nicol JW;Helt GA;Blanchard SG Jr;Raja A;Loraine AE
通讯作者：
Loraine AE
影响因子：
16.8
作者：
Lerdrup, Mads;Johansen, Jens Vilstrup;Hansen, Klaus
通讯作者：
Hansen, Klaus
影响因子：
64.8
作者：
Obri, Arnaud;Ouararhni, Khalid;Hamiche, Ali
通讯作者：
Hamiche, Ali
影响因子：
3.7
作者：
Binda, Olivier;Sevilla, Ana;Richard, Stephane
通讯作者：
Richard, Stephane
影响因子：
4.5
作者：
Coleman-Derr D;Zilberman D
通讯作者：
Zilberman D