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...

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Autores principales:	Tanvir Alam, Yulia A Medvedeva, Hui Jia, James B Brown, Leonard Lipovich, Vladimir B Bajic
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9436a7bc1fb436a9c89f0e4e5662b4b
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spelling	oai:doaj.org-article:d9436a7bc1fb436a9c89f0e4e5662b4b2021-11-25T05:58:15ZPromoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.1932-620310.1371/journal.pone.0109443https://doaj.org/article/d9436a7bc1fb436a9c89f0e4e5662b4b2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0109443https://doaj.org/toc/1932-6203Transcriptional 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.Tanvir AlamYulia A MedvedevaHui JiaJames B BrownLeonard LipovichVladimir B BajicPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e109443 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tanvir Alam Yulia A Medvedeva Hui Jia James B Brown Leonard Lipovich Vladimir B Bajic Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
description	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.
format	article
author	Tanvir Alam Yulia A Medvedeva Hui Jia James B Brown Leonard Lipovich Vladimir B Bajic
author_facet	Tanvir Alam Yulia A Medvedeva Hui Jia James B Brown Leonard Lipovich Vladimir B Bajic
author_sort	Tanvir Alam
title	Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
title_short	Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
title_full	Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
title_fullStr	Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
title_full_unstemmed	Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
title_sort	promoter analysis reveals globally differential regulation of human long non-coding rna and protein-coding genes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d9436a7bc1fb436a9c89f0e4e5662b4b
work_keys_str_mv	AT tanviralam promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes AT yuliaamedvedeva promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes AT huijia promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes AT jamesbbrown promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes AT leonardlipovich promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes AT vladimirbbajic promoteranalysisrevealsgloballydifferentialregulationofhumanlongnoncodingrnaandproteincodinggenes
_version_	1718414371301883904

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

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