A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
biocq 添加于 2012-3-25 14:28
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作 者
Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY 摘 要
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.-
详细资料
- 关键词: Animals; Cell Line; Cells, Cultured; Chromatin/*genetics/metabolism; DNA, Intergenic/genetics; Embryo, Mammalian/metabolism; Fibroblasts/metabolism; Gene Expression Regulation, Developmental/*genetics; Gene Knockdown Techniques; Genes, Homeobox/*genetics; Histone-Lysine N-Methyltransferase/metabolism; Histones/chemistry/metabolism; Humans; Lysine/metabolism; Methylation; Mice; Molecular Sequence Data; Multigene Family/genetics; Organ Specificity; RNA, Untranslated/*genetics; Transcription, Genet ...
- 文献种类: Journal Article
- 期刊名称: Nature
- 期刊缩写: Nature
- 期卷页: 2011年 第472卷 第7341期 120-124页
- 地址: Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA
- ISBN: 0028-0836
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A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
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学科领域 生物医药 » 生物学
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