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PMID: 17604720 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.

Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs.

Cell ·Vol. 129 ·No. 7 ·2007-06-29 ·Pages 1311-23

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY

Abstract

Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.

MeSH Terms
Animals Base Sequence/genetics Body Patterning/genetics Cells, Cultured Chromatin/genetics DNA Methylation Embryonic Development/genetics Epigenesis, Genetic/genetics Gene Expression Regulation, Developmental/genetics Genes, Homeobox/genetics Histones/genetics Humans Mice Mice, Inbred C57BL Molecular Sequence Data Polycomb-Group Proteins RNA Interference/physiology RNA, Untranslated/chemistry,genetics Regulatory Elements, Transcriptional/genetics Repressor Proteins/genetics
Chemicals
Chromatin Histones Polycomb-Group Proteins RNA, Untranslated Repressor Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Rinn John L
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kertesz Michael
Wang Jordon K
Squazzo Sharon L
Xu Xiao
Brugmann Samantha A
Goodnough L Henry
Helms Jill A
Farnham Peggy J
Segal Eran
Chang Howard Y
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.05.022
Published
2007-06-29
Pages
1311-23
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2084369
Subset
IM
Grants
NIAMS NIH HHS · K08 AR050007 · United States
NIAMS NIH HHS · K08 AR050007-03 · United States
NCI NIH HHS · R01 CA119176 · United States
NCI NIH HHS · R01 CA119176-02 · United States
Databases
GENBANK
DQ926657
Corrections
CommentIn
PMID: 17604716
External Links
PubMed source DOI: 10.1016/j.cell.2007.05.022 PMC Full Text View journal details
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