通过染色质重塑对小鼠乳腺肿瘤病毒启动子进行转录沉默与M期组蛋白H1磷酸化和组蛋白H3过度磷酸化同时发生。

Transcriptional silencing of the mouse mammary tumor virus promoter through chromatin remodeling is concomitant with histone H1 phosphorylation and histone H3 hyperphosphorylation at M phase.

作者信息

Bhattacharjee Rabindra N, Archer Trevor K

机构信息

Department of Obstetrics and Gynaecology, University of Western Ontario, London, ON, Canada N6A 4L6.

出版信息

Virology. 2006 Mar 1;346(1):1-6. doi: 10.1016/j.virol.2005.12.034. Epub 2006 Feb 3.

DOI:10.1016/j.virol.2005.12.034

PMID:16458342

Abstract

We examined histone phosphorylation and their effects on glucocorticoid receptor (GR)-mediated activation of the mouse mammary tumor virus promoter (MMTV) in synchronized cells. In vivo protein expression studies suggest that both histones H1 and H3 are highly phosphorylated in mitotic-arrested cells in which GR is unable to remodel chromatin and recruit transcription factor NF1 to the promoter. Postmitotic cells show an open chromatin structure and efficient binding of NF1 to the promoter accompanied by reversing histone H1 and H3 phosphorylation level. In contrast, the acetylation status of histone H3 and H4 did not change in either condition. These results suggest that hyperphosphorylation of histone H1 and H3 leads to inhibition of GR-mediated chromatin remodeling and inactivation of MMTV by preventing the association of transcription factors to the promoter in vivo.

摘要

我们研究了组蛋白磷酸化及其对同步化细胞中糖皮质激素受体（GR）介导的小鼠乳腺肿瘤病毒启动子（MMTV）激活的影响。体内蛋白质表达研究表明，在有丝分裂停滞的细胞中，组蛋白H1和H3均高度磷酸化，在这类细胞中GR无法重塑染色质并将转录因子NF1募集至启动子。有丝分裂后的细胞呈现开放的染色质结构，NF1与启动子有效结合，同时组蛋白H1和H3的磷酸化水平逆转。相比之下，在这两种情况下组蛋白H3和H4的乙酰化状态均未改变。这些结果表明，组蛋白H1和H3的过度磷酸化通过阻止转录因子在体内与启动子结合，导致GR介导的染色质重塑受到抑制以及MMTV失活。