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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Hsieh CL,Lin CL,Liu H,Chang YJ,Shih CJ,Zhong CZ,Lee SC,Tan BC

doi

10.1093/nar/gkq1338

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

4048-62

issue

10

eissn

0305-1048

issn

1362-4962

pii

gkq1338

journal_volume

39

pub_type

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