Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.

We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene express...

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Autores principales:	Andrew T Kwon, Alice Yi Chou, David J Arenillas, Wyeth W Wasserman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c9a710453c5402face97518a5837cbf
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spelling	oai:doaj.org-article:6c9a710453c5402face97518a5837cbf2021-11-18T05:51:46ZValidation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.1553-734X1553-735810.1371/journal.pcbi.1002256https://doaj.org/article/6c9a710453c5402face97518a5837cbf2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22144875/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions.Andrew T KwonAlice Yi ChouDavid J ArenillasWyeth W WassermanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 12, p e1002256 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andrew T Kwon Alice Yi Chou David J Arenillas Wyeth W Wasserman Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
description	We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions.
format	article
author	Andrew T Kwon Alice Yi Chou David J Arenillas Wyeth W Wasserman
author_facet	Andrew T Kwon Alice Yi Chou David J Arenillas Wyeth W Wasserman
author_sort	Andrew T Kwon
title	Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
title_short	Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
title_full	Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
title_fullStr	Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
title_full_unstemmed	Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
title_sort	validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6c9a710453c5402face97518a5837cbf
work_keys_str_mv	AT andrewtkwon validationofskeletalmusclecisregulatorymodulepredictionsrevealsnucleotidecompositionbiasinfunctionalenhancers AT aliceyichou validationofskeletalmusclecisregulatorymodulepredictionsrevealsnucleotidecompositionbiasinfunctionalenhancers AT davidjarenillas validationofskeletalmusclecisregulatorymodulepredictionsrevealsnucleotidecompositionbiasinfunctionalenhancers AT wyethwwasserman validationofskeletalmusclecisregulatorymodulepredictionsrevealsnucleotidecompositionbiasinfunctionalenhancers
_version_	1718424732918874112

Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.

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