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PMID:21266480
| 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 |
| edit table |
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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