title: Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells.
abstract: The clustered Hox genes, which are highly conserved across metazoans, encode homeodomain-containing transcription factors that provide a blueprint for segmental identity along the body axis. Recent studies have underscored that in addition to encoding Hox genes, the homeotic clusters contain key noncoding RNA genes that play a central role in development. In this study, we have taken advantage of genome-wide approaches to provide a detailed analysis of retinoic acid (RA)-induced transcriptional and epigenetic changes within the homeotic clusters of mouse embryonic stem cells. Although there is a general colinear response, our analyses suggest a lack of strict colinearity for several genes in the HoxA and HoxB clusters. We have identified transcribed novel noncoding RNAs (ncRNAs) and their cis-regulatory elements that function in response to RA and demonstrated that the expression of these ncRNAs from both strands represent some of the most rapidly induced transcripts in ES cells. Finally, we have provided dynamic analyses of chromatin modifications for the coding and noncoding genes expressed upon activation and suggest that active transcription can occur in the presence of chromatin modifications and machineries associated with repressed transcription state over the clusters. Overall, our data provide a resource for a better understanding of the dynamic nature of the coding and noncoding transcripts and their associated chromatin marks in the regulation of homeotic gene transcription during development.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Bony
authors.initials: B
authors.lastname: De Kumar
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Mark E
authors.initials: ME
authors.lastname: Parrish
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Madelaine
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidel
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Ariel
authors.initials: A
authors.lastname: Paulson
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Karin
authors.initials: K
authors.lastname: Gaudenz
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Allison
authors.initials: A
authors.lastname: Peak
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: William
authors.initials: W
authors.lastname: McDowell
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Brian
authors.initials: B
authors.lastname: Fleharty
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Youngwook
authors.initials: Y
authors.lastname: Ahn
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Chengqi
authors.initials: C
authors.lastname: Lin
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Edwin
authors.initials: E
authors.lastname: Smith
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D022661:RNA, Untranslated / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D022661:RNA, Untranslated; D014212:Tretinoin