Linked Life Data

14673137

Source:http://linkedlifedata.com/resource/pubmed/id/14673137

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-1
pubmed:abstractText
The human GH gene family is specifically expressed in somatotrophs of the anterior pituitary and placental syncytiotrophoblast. Two nuclease-hypersensitive sites, HS III and HS V, are associated with a region of chromatin located 28 and 30 kb upstream of the pituitary GH gene transcription initiation site (+1) in both pituitary and placenta nuclei. A role for this region in pituitary GH gene expression has been reported, but the potential relevance to placental gene expression has not been determined. Deletion analysis of a 5.2-kb region (nucleotides - 27,568/-32,746) containing HS III to V-related sequences localized significant enhancer activity to a 574-bp HS III fragment (nucleotides -27,676/-28,249) in multiple transfected cell lines. Four nuclease-protected regions [footprints (FP) 1-4] were identified in the 574-bp fragment. FP2 and FP3 were detected with placenta cell nuclear protein, whereas FP1 and FP4 were observed with placental and nonplacental cell nuclear extract. Disruption of FP1 had no effect on heterologous promoter activity in transfected pituitary and placental cells, whereas loss of FP2 and FP3 resulted in modest increases in placental cells, reflecting the presence of repressor activity associated with these regions in vitro. In contrast, disruption of the FP4 region by mutation or deletion significantly reduced enhancer activity. As a result, 30-fold enhancer activity was localized to a 41-bp region in transfected placental tumor cells. Binding of candidate proteins, activator protein (AP)-2 (FP3) and Elk-1 (FP4), was confirmed using competition assays with specific oligonucleotides and antibodies. Moreover, these factors were associated with the hyperacetylated HS III region in human pituitary [activator protein 2 (AP-2) and Elk-1] and term placenta (AP-2) chromatin. These data implicate AP-2 and ETS-domain family members in the regulation of the GH/CS locus and raise the possibility that different complexes form in the HS III region in placenta and pituitary cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
574-87
pubmed:dateRevised
2010-6-7
pubmed:meshHeading
pubmed-meshheading:14673137-Acetylation, pubmed-meshheading:14673137-Base Sequence, pubmed-meshheading:14673137-Binding Sites, pubmed-meshheading:14673137-Cell Line, pubmed-meshheading:14673137-Chromatin, pubmed-meshheading:14673137-DNA, pubmed-meshheading:14673137-DNA-Binding Proteins, pubmed-meshheading:14673137-Enhancer Elements, Genetic, pubmed-meshheading:14673137-Female, pubmed-meshheading:14673137-Human Growth Hormone, pubmed-meshheading:14673137-Humans, pubmed-meshheading:14673137-Molecular Sequence Data, pubmed-meshheading:14673137-Mutation, pubmed-meshheading:14673137-Pituitary Gland, pubmed-meshheading:14673137-Placenta, pubmed-meshheading:14673137-Placental Lactogen, pubmed-meshheading:14673137-Pregnancy, pubmed-meshheading:14673137-Protein Structure, Tertiary, pubmed-meshheading:14673137-Proto-Oncogene Proteins, pubmed-meshheading:14673137-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:14673137-Transcription Factor AP-2, pubmed-meshheading:14673137-Transcription Factors, pubmed-meshheading:14673137-ets-Domain Protein Elk-1
pubmed:year
2004
pubmed:articleTitle
Binding of AP-2 and ETS-domain family members is associated with enhancer activity in the hypersensitive site III region of the human growth hormone/chorionic somatomammotropin locus.
pubmed:affiliation
Department of Physiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 3J7.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't