Publication Date:
2008-11-01
Description:
To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748911/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748911/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Jing -- Sun, Bryan K -- Erwin, Jennifer A -- Song, Ji-Joon -- Lee, Jeannie T -- R01 GM058839/GM/NIGMS NIH HHS/ -- R01 GM058839-10/GM/NIGMS NIH HHS/ -- R01 GM110090/GM/NIGMS NIH HHS/ -- R01GM58839/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):750-6. doi: 10.1126/science.1163045.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974356" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
Cell Line
;
Chromatin Immunoprecipitation
;
Electrophoretic Mobility Shift Assay
;
Embryonic Stem Cells
;
Female
;
Fibroblasts
;
Male
;
Mice
;
Mice, Transgenic
;
Molecular Sequence Data
;
Polycomb-Group Proteins
;
Polymerase Chain Reaction
;
RNA, Long Noncoding
;
RNA, Untranslated/genetics/*metabolism
;
Repetitive Sequences, Nucleic Acid
;
Repressor Proteins/*metabolism
;
Up-Regulation
;
X Chromosome/*metabolism
;
X Chromosome Inactivation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
