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A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
Authors
Wang, Kevin C.Yang, Yul W.
Liu, Bo
Sanyal, Amartya
Corces-Zimmerman, Ryan
Chen, Yong
Lajoie, Bryan R.
Protacio, Angeline
Flynn, Ryan A.
Gupta, Rajnish A.
Wysocka, Joanna
Lei, Ming
Dekker, Job
Helms, Jill A.
Chang, Howard Y.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2011-04-07Keywords
AnimalsCell Line
Cells, Cultured
Chromatin
DNA, Intergenic
Embryo, Mammalian
Fibroblasts
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Genes, Homeobox
Histone-Lysine N-Methyltransferase
Histones
Humans
Lysine
Methylation
Mice
Molecular Sequence Data
Multigene Family
Organ Specificity
RNA, Untranslated
Transcription, Genetic
Genetics and Genomics
Metadata
Show full item recordAbstract
The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing. Potential roles of lincRNAs in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control. Some locus control elements and enhancers transcribe lincRNAs, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5'of the cluster. Here we identify HOTTIP, a lincRNA transcribed from the 5' tip of the HOXA locus that coordinates the activation of several 5' HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.Source
Nature. 2011 Apr 7;472(7341):120-4. Epub 2011 Mar 20. Link to article on publisher's siteDOI
10.1038/nature09819Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43953PubMed ID
21423168Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nature09819