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PMID:21266480

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Citation

Hsieh, CL, Lin, CL, Liu, H, Chang, YJ, Shih, CJ, Zhong, CZ, Lee, SC and Tan, BC (2011) WDHD1 modulates the post-transcriptional step of the centromeric silencing pathway. Nucleic Acids Res. 39:4048-62

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.

Links

PubMed PMC3105424 Online version:10.1093/nar/gkq1338

Keywords

Animals; Cell Cycle; Cell Line; Centromere/chemistry; Centromere/metabolism; DNA-Binding Proteins/analysis; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/physiology; Down-Regulation; Epigenesis, Genetic; Gene Silencing; Heterochromatin/chemistry; Humans; Mice; RNA Processing, Post-Transcriptional; S Phase; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WDHD1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WDHD1

enables

GO:0003723: RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WDHD1

located_in

GO:0000775: chromosome, centromeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:WDHD1

enables

GO:0070063: RNA polymerase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WDHD1

involved_in

GO:0140462: pericentric heterochromatin organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WDHD1

involved_in

GO:0006396: RNA processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WDHD1

involved_in

GO:0033044: regulation of chromosome organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WDHD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q99MU3

F

Seeded From UniProt

complete

MOUSE:DSRAD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P59328

F

Seeded From UniProt

complete


See also

References

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