Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7351
pubmed:dateCreated
2011-6-16
pubmed:databankReference
pubmed:abstractText
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA) based on global nuclear run-on sequencing (GRO-seq) analysis, with a unique class apparently requiring no nucleosome remodelling to induce specific enhancer-promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/, http://linkedlifedata.com/resource/pubmed/grant/DK01847, http://linkedlifedata.com/resource/pubmed/grant/DK074868, http://linkedlifedata.com/resource/pubmed/grant/DK37949, http://linkedlifedata.com/resource/pubmed/grant/GM049369, http://linkedlifedata.com/resource/pubmed/grant/HG004659, http://linkedlifedata.com/resource/pubmed/grant/NS34934, http://linkedlifedata.com/resource/pubmed/grant/P01 DK074868-05, http://linkedlifedata.com/resource/pubmed/grant/R01 CA097134-10, http://linkedlifedata.com/resource/pubmed/grant/R01 DK018477-35, http://linkedlifedata.com/resource/pubmed/grant/R01 DK039949-30, http://linkedlifedata.com/resource/pubmed/grant/R01 GM049369-17, http://linkedlifedata.com/resource/pubmed/grant/R01 HG004659-03, http://linkedlifedata.com/resource/pubmed/grant/R01 HL065445-12, http://linkedlifedata.com/resource/pubmed/grant/R01 NS034934-23, http://linkedlifedata.com/resource/pubmed/grant/R37 DK039949-28, http://linkedlifedata.com/resource/pubmed/grant/R37 DK039949-30
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
474
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
390-4
pubmed:dateRevised
2011-10-21
pubmed:meshHeading
pubmed-meshheading:21572438-Base Sequence, pubmed-meshheading:21572438-Cell Line, Tumor, pubmed-meshheading:21572438-Cell Lineage, pubmed-meshheading:21572438-Dihydrotestosterone, pubmed-meshheading:21572438-Down-Regulation, pubmed-meshheading:21572438-Enhancer Elements, Genetic, pubmed-meshheading:21572438-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21572438-Gene Knockdown Techniques, pubmed-meshheading:21572438-Genome, Human, pubmed-meshheading:21572438-HEK293 Cells, pubmed-meshheading:21572438-Hepatocyte Nuclear Factor 3-alpha, pubmed-meshheading:21572438-Histones, pubmed-meshheading:21572438-Humans, pubmed-meshheading:21572438-Kallikreins, pubmed-meshheading:21572438-Male, pubmed-meshheading:21572438-Prostatic Neoplasms, pubmed-meshheading:21572438-RNA, Small Interfering, pubmed-meshheading:21572438-RNA, Untranslated, pubmed-meshheading:21572438-Receptors, Androgen, pubmed-meshheading:21572438-Transcription, Genetic
pubmed:year
2011
pubmed:articleTitle
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
pubmed:affiliation
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural