Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

Handle URI:
http://hdl.handle.net/10754/334972
Title:
Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes
Authors:
Alam, Tanvir ( 0000-0003-4844-0171 ) ; Medvedeva, Yulia A.; Jia, Hui; Brown, James B.; Lipovich, Leonard; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
Abstract:
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 of 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.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Alam T, Medvedeva YA, Jia H, Brown JB, Lipovich L, et al. (2014) Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes. PLoS ONE 9(10): e109443. doi:10.1371/journal.pone.0109443
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
Issue Date:
2-Oct-2014
DOI:
10.1371/journal.pone.0109443
PubMed ID:
25275320
PubMed Central ID:
PMC4183604
Type:
Article
ISSN:
1932-6203
Sponsors:
TA and VBB were supported by KAUST Base Research Fund to VBB. LL was supported by the ENCODE Consortium through NIH 1U01-HG007031 to Peter Bickel, University of California, Berkeley. JBB's work was supported by NHGRI K99 HG006698. HJ was supported by the Wayne State University Perinatal Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Additional Links:
http://dx.plos.org/10.1371/journal.pone.0109443
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAlam, Tanviren
dc.contributor.authorMedvedeva, Yulia A.en
dc.contributor.authorJia, Huien
dc.contributor.authorBrown, James B.en
dc.contributor.authorLipovich, Leonarden
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-11-16T08:31:09Z-
dc.date.available2014-11-16T08:31:09Z-
dc.date.issued2014-10-02en
dc.identifier.citationAlam T, Medvedeva YA, Jia H, Brown JB, Lipovich L, et al. (2014) Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes. PLoS ONE 9(10): e109443. doi:10.1371/journal.pone.0109443en
dc.identifier.issn1932-6203en
dc.identifier.pmid25275320en
dc.identifier.doi10.1371/journal.pone.0109443en
dc.identifier.urihttp://hdl.handle.net/10754/334972en
dc.description.abstractTranscriptional 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 of 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.en
dc.description.sponsorshipTA and VBB were supported by KAUST Base Research Fund to VBB. LL was supported by the ENCODE Consortium through NIH 1U01-HG007031 to Peter Bickel, University of California, Berkeley. JBB's work was supported by NHGRI K99 HG006698. HJ was supported by the Wayne State University Perinatal Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0109443en
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectChromatinen
dc.subjectDNA methylationen
dc.subjectDNA transcriptionen
dc.subjectGene expressionen
dc.subjectGene regulationen
dc.subjectLong non-coding RNAsen
dc.subjectSequence motif analysisen
dc.subjectTranscription factorsen
dc.titlePromoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genesen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC4183604en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCenter for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of Americaen
dc.contributor.institutionDepartment of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of Americaen
dc.contributor.institutionDepartment of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States of Americaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAlam, Tanviren
kaust.authorMedvedeva, Yuliaen
kaust.authorBajic, Vladimir B.en

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