Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs

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 kil...

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Veröffentlicht in:Cell 2007-06, Vol.129 (7), p.1311-1323
Hauptverfasser: Rinn, John L., 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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container_end_page 1323
container_issue 7
container_start_page 1311
container_title Cell
container_volume 129
creator Rinn, John L.
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.
description 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.
doi_str_mv 10.1016/j.cell.2007.05.022
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source MEDLINE; ScienceDirect Journals (5 years ago - present); Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects 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
Regulatory Elements, Transcriptional - genetics
Repressor Proteins - genetics
RNA Interference - physiology
RNA, Untranslated - chemistry
RNA, Untranslated - genetics
title Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
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