WDHD1 modulates the post-transcriptional step of the centromeric silencing pathway

Chia Ling Hsieh, Chih Li Lin, Hsuan Liu, Yao Jen Chang, Chii Jiun Shih, Chang Zheng Zhong, Sheng Chung Lee, Bertrand Chin Ming Tan

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37 引文 斯高帕斯(Scopus)

摘要

The centromere is a highly specialized chromosomal element that is essential for chromosome segregation during mitosis. Centromere integrity must therefore be properly preserved and is strictly dependent upon the establishment and maintenance of surrounding chromatin structure. Here we identify WDHD1, a WD40-domain and HMG-domain containing protein, as a key regulator of centromere function. We show that WDHD1 associates with centromeres in a cell cycle-dependent manner, coinciding with mid-to-late S phase. WDHD1 down-regulation compromises HP1α localization to pericentric heterochromatin and leads to altered expression of epigenetic markers associated with this chromatin region. As a consequence, such reduced epigenetic silencing is manifested in disrupted heterochromatic state of the centromere and a defective mitosis. Moreover, we demonstrate that a possible underlying mechanism of WDHD1's involvement lies in the proper generation of the small non-coding RNAs encoded by the centromeric satellite repeats. This role is mediated at the post-transcriptional level and likely through stabilizing Dicer association with centromeric RNA. Collectively, these findings suggest that WDHD1 may be a critical component of the RNA-dependent epigenetic control mechanism that sustains centromere integrity and genomic stability.
原文英語
頁(從 - 到)4048-4062
頁數15
期刊Nucleic Acids Research
39
發行號10
DOIs
出版狀態已發佈 - 5月 2011
對外發佈

ASJC Scopus subject areas

  • 遺傳學

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