Linked Life Data

20664054

Source:http://linkedlifedata.com/resource/pubmed/id/20664054

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-11-12
pubmed:abstractText
The nuclear factor of activated T cells (NFAT) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for cell growth and survival in hematopoietic cells. Recent experimental evidence has implicated the calcineurin/NFAT signaling pathway in the pathogenesis of various malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the molecular mechanism(s) underlying NFATc1 regulation of genes controlling lymphoma cell growth and survival is still unclear. In this study, we demonstrate that the transcription factor NFATc1 regulates gene expression in DLBCL cells through a chromatin remodeling mechanism that involves recruitment of the SWItch/Sucrose NonFermentable chromatin remodeling complex ATPase enzyme SMARCA4 (also known as Brahma-related gene 1) to NFATc1 targeted gene promoters. The NFATc1/Brahma-related gene 1 complex induces promoter DNase I hypersensitive sites and recruits other transcription factors to the active chromatin site to regulate gene transcription. Targeting NFATc1 with specific small hairpin RNA inhibits DNase I hypersensitive site formation and down-regulates target gene expression. Our data support a novel epigenetic control mechanism for the transcriptional regulation of growth and survival genes by NFATc1 in the pathophysiology of DLBCL and suggests that targeting NFATc1 could potentially have therapeutic value.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3899-906
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed-meshheading:20664054-Base Sequence, pubmed-meshheading:20664054-Cell Line, Tumor, pubmed-meshheading:20664054-Cell Proliferation, pubmed-meshheading:20664054-Cell Survival, pubmed-meshheading:20664054-Chromatin Assembly and Disassembly, pubmed-meshheading:20664054-DNA Helicases, pubmed-meshheading:20664054-DNA Primers, pubmed-meshheading:20664054-Deoxyribonuclease I, pubmed-meshheading:20664054-Epigenesis, Genetic, pubmed-meshheading:20664054-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20664054-Genes, myc, pubmed-meshheading:20664054-Humans, pubmed-meshheading:20664054-Lymphoma, Large B-Cell, Diffuse, pubmed-meshheading:20664054-Models, Biological, pubmed-meshheading:20664054-NFATC Transcription Factors, pubmed-meshheading:20664054-Nuclear Proteins, pubmed-meshheading:20664054-Promoter Regions, Genetic, pubmed-meshheading:20664054-RNA, Small Interfering, pubmed-meshheading:20664054-Transcription, Genetic, pubmed-meshheading:20664054-Transcription Factors
pubmed:year
2010
pubmed:articleTitle
An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas.
pubmed:affiliation
Department of Hematopathology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. lvpham@mdanderson.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural