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Title: Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes

Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently ofmore » mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.« less
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [5]
  1. King Abdullah University of Science and Technology (KAUST), Thuwal (Saudi Arabia)
  2. Wayne State Univ., Detroit, MI (United States). Center for Molecular Medicine and Genetics.
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Department of Genome Dynamics, Life Sciences Division.
  4. Wayne State Univ., Detroit, MI (United States). Center for Molecular Medicine and Genetics and Dept. of Neurology.
  5. Universita` degli Studi di Milano (Italy)
Publication Date:
OSTI Identifier:
1212466
Grant/Contract Number:
AC02-05CH11231
Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 9; Journal Issue: 10; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE; National Institute of Health
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES long non-coding RNAs; gene regulation; chromatin; DNA transcription; gene expression; sequence motif analysis; transcription factors; DNA methylation