Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2007-10-8
pubmed:abstractText
The RE-1 silencer of transcription (REST) is a transcriptional regulator that represses neuron-specific genes in non-neuronal tissues by remodeling chromatin structure. We have utilized human mesenchymal stem cells (MSCs) as a research tool to understand the molecular mechanisms that regulate a neurogenic program of differentiation in non-neuronal tissue. MSCs are mesoderm-derived cells that generate specialized cells such as stroma, fat, bone, and cartilage. We have reported previously the transdifferentiation of MSCs into functional neuronal cells (Cho, K. J., Trzaska, K. A., Greco, S. J., McArdle, J., Wang, F. S., Ye, J.-H., and Rameshwar, P. (2005) Stem Cells 23, 383-391). Expression of the neurotransmitter gene TAC1 was detected only in neuronal cells and thus served as a model to study transcriptional regulation of neuron-specific genes in undifferentiated MSCs. Bone marrow stromal cells are known to transiently express TAC1 following stimulation with the microenvironmental factor interleukin-1alpha. We thus compared the effects of interleukin-1alpha stimulation and neuronal induction of MSCs on TAC1 regulation. Transcription factor mapping of the 5'-flanking region of the TAC1 promoter predicted two REST-binding sites adjacent to one NFkappaB site within exon 1. Chromatin immunoprecipitation, mutagenesis, and loss-of-function studies showed that both transcription factors synergistically mediated repression of TAC1 in the neurogenic and microenvironmental models. Together, the results support the novel finding of synergism between REST and NFkappaB in the suppression of TAC1 in non-neuronal cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30039-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Synergy between the RE-1 silencer of transcription and NFkappaB in the repression of the neurotransmitter gene TAC1 in human mesenchymal stem cells.
pubmed:affiliation
Department of Medicine, Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't