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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4048-4062
Number of pages15
JournalNucleic Acids Research
Volume39
Issue number10
DOIs
Publication statusPublished - May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'WDHD1 modulates the post-transcriptional step of the centromeric silencing pathway'. Together they form a unique fingerprint.

  • Cite this

    Hsieh, C. L., Lin, C. L., Liu, H., Chang, Y. J., Shih, C. J., Zhong, C. Z., Lee, S. C., & Tan, B. C. M. (2011). WDHD1 modulates the post-transcriptional step of the centromeric silencing pathway. Nucleic Acids Research, 39(10), 4048-4062. https://doi.org/10.1093/nar/gkq1338