Linked Life Data

12952189

Source:http://linkedlifedata.com/resource/pubmed/id/12952189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-9-3
pubmed:abstractText
Key components of the basal transcription machinery and several tissue-specific transcription factor complexes are functionally compartmentalized as specialized subnuclear domains. We have identified a unique 31-38 amino acid targeting signal (NMTS) that directs the Runx (Cbfa/AML) transcription factors to distinct nuclear matrix-(NM) associated sites within the nucleus that support gene expression. Our determination of the NMTS crystal structure, yeast 2 hybrid screens to identify NM interacting proteins, and in situ colocalization studies with Runx interacting factors (YAP, Smad, TLE) suggest that localization of Runx transcription factors at intranuclear sites facilitates the assembly and activity of regulatory complexes that mediate activation and suppression of target genes. Mice homozygous for the deletion of the intranuclear Runx2 targeting signal in a homologous recombination (Runx2 deltaC) do not form bone due to maturational arrest of osteoblasts, demonstrating the importance of fidelity of subnuclear localization for tissue-differentiating activity. These results provide evidence that Runx2 subnuclear targeting and the associated regulatory functions are essential for a spatiotemporal placement that facilitates activation of Runx-dependent genes involved in tissue differentiation during embryonic development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-8207
pubmed:author
pubmed:issnType
Print
pubmed:volume
44 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Temporal and spatial parameters of skeletal gene expression: targeting RUNX factors and their coregulatory proteins to subnuclear domains.
pubmed:affiliation
Department of Cell Biology, University of Massachusetts Cancer Center, Worcester, Massachusetts 01655, USA. gary.stein@umassmed.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review