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PMID: 19164542 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

X chromosome inactivation in the absence of Dicer.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 106 ·No. 4 ·2009-01-27 ·Pages 1122-7

Kanellopoulou C, Muljo SA, Dimitrov SD, Chen X, Colin C, Plath K, Livingston DM

Abstract

Dicer is central to the RNA interference (RNAi) pathway, because it is required for processing of double-stranded RNA (dsRNA) precursors into small RNA effector molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The X inactive specific transcript (Xist) is an untranslated RNA that is required for dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in female cells and initiates a chromosomewide change in chromatin structure that includes the recruitment of Polycomb proteins, but it is largely unknown how Xist RNA mediates these processes. To investigate a potential link between the RNAi pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation had modest effects on the steady-state levels of spliced Xist RNA. Together our data indicate that the RNAi machinery is not essential for the initiation of X inactivation.

MeSH Terms
Animals Crosses, Genetic DEAD-box RNA Helicases/deficiency,metabolism Doxycycline/pharmacology Embryonic Stem Cells/cytology,drug effects,metabolism Endoribonucleases/deficiency,metabolism Female Gene Silencing/drug effects Genes, X-Linked Inbreeding Male Mice Mice, Inbred C57BL Mice, Knockout Models, Genetic Polycomb-Group Proteins RNA, Long Noncoding RNA, Untranslated/metabolism Repressor Proteins/metabolism Ribonuclease III Tetracycline/pharmacology X Chromosome/genetics X Chromosome Inactivation/drug effects,genetics
Chemicals
Polycomb-Group Proteins RNA, Long Noncoding RNA, Untranslated Repressor Proteins XIST non-coding RNA Endoribonucleases Dicer1 protein, mouse Ribonuclease III DEAD-box RNA Helicases Tetracycline Doxycycline
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kanellopoulou Chryssa
Dana-Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA.
Muljo Stefan A
Dimitrov Stoil D
Chen Xi
Colin Christian
Plath Kathrin
Livingston David M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0812210106
Published
2009-01-27
Epub
2009-00-21
Pages
1122-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2633553
Subset
IM
Grants
NIAID NIH HHS · F32 AI060302 · United States
NIAID NIH HHS · R01 AI064345 · United States
NIAID NIH HHS · AI-060302 · United States
NIAID NIH HHS · R01 AI-064345 · United States
External Links
PubMed source DOI: 10.1073/pnas.0812210106 PMC Full Text View journal details
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