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PMID: 22078878 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs.

Cell ·Vol. 147 ·No. 4 ·2011-11-11 ·Pages 773-88

Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC, Rosenfeld MG

Abstract

Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs.

MeSH Terms
Amino Acid Sequence Cell Line Cell Nucleus/metabolism Chromatin/metabolism E2F1 Transcription Factor/metabolism Gene Expression Regulation HeLa Cells Humans Ligases Methylation Methyltransferases/metabolism Molecular Sequence Data Polycomb-Group Proteins RNA, Long Noncoding RNA, Untranslated/metabolism Repressor Proteins/chemistry,metabolism Sumoylation Transcription, Genetic Ubiquitin-Protein Ligases Ubiquitination
Chemicals
CDCA7L protein, human Chromatin E2F1 Transcription Factor E2F1 protein, human MALAT1 long non-coding RNA, human Polycomb-Group Proteins RNA, Long Noncoding RNA, Untranslated Repressor Proteins SUV39H1 protein, human Methyltransferases Ubiquitin-Protein Ligases Ligases CBX4 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yang Liuqing
Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.
Lin Chunru
Liu Wen
Zhang Jie
Ohgi Kenneth A
Grinstein Jonathan D
Dorrestein Pieter C
Rosenfeld Michael G
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2011.08.054
Published
2011-11-11
Pages
773-88
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3297197
Subset
IM
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NIDDK NIH HHS · R37 DK039949-30 · United States
NIDDK NIH HHS · R01 DK018477-37 · United States
NIDDK NIH HHS · P01 DK074868 · United States
NIDDK NIH HHS · DK018477 · United States
NIDDK NIH HHS · R37 DK039949 · United States
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NIDDK NIH HHS · R01 DK018477-35 · United States
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NIDDK NIH HHS · R01 DK018477 · United States
NIDDK NIH HHS · R01 DK039949 · United States
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NIDDK NIH HHS · R01 DK039949-17S1 · United States
NCI NIH HHS · CA97134 · United States
NINDS NIH HHS · NS34934 · United States
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NHLBI NIH HHS · R01 HL065445 · United States
NIDDK NIH HHS · DK39949 · United States
NINDS NIH HHS · R01 NS034934-23 · United States
NCI NIH HHS · R01 CA097134-10 · United States
NCI NIH HHS · R01 CA097134 · United States
Howard Hughes Medical Institute · United States
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PMID: 22166993
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PubMed source DOI: 10.1016/j.cell.2011.08.054 PMC Full Text View journal details
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