Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-7-14
pubmed:abstractText
DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1-/- NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3345-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16014513-Animals, pubmed-meshheading:16014513-Astrocytes, pubmed-meshheading:16014513-Base Sequence, pubmed-meshheading:16014513-Brain, pubmed-meshheading:16014513-Cell Differentiation, pubmed-meshheading:16014513-DNA (Cytosine-5-)-Methyltransferase, pubmed-meshheading:16014513-DNA Methylation, pubmed-meshheading:16014513-DNA Primers, pubmed-meshheading:16014513-Gene Expression Regulation, Developmental, pubmed-meshheading:16014513-Genes, Reporter, pubmed-meshheading:16014513-In Situ Nick-End Labeling, pubmed-meshheading:16014513-Mice, pubmed-meshheading:16014513-Mice, Knockout, pubmed-meshheading:16014513-Mice, Transgenic, pubmed-meshheading:16014513-Rats, pubmed-meshheading:16014513-Signal Transduction, pubmed-meshheading:16014513-Stem Cells, pubmed-meshheading:16014513-Trans-Activators, pubmed-meshheading:16014513-Transfection
pubmed:year
2005
pubmed:articleTitle
DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling.
pubmed:affiliation
Department of Human Genetics, University of California at Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095, USA. gfan@mednet.ucla.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural