Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-5-17
pubmed:abstractText
Follistatin was originally identified as a specific inhibitor of follicle stimulating hormone secretion and later characterized as a binding protein for activin. Since activin regulates hormone secretion and cell differentiation, the importance of understanding the mechanisms regulating the synthesis of its binding protein, follistatin, is evident. To study the regulation of follistatin gene expression, we first determined the transcription start site (cap site) of the rat follistatin gene using primer extension and ribonuclease protection assay. Our results led to the identification of multiple cap sites located at three different positions of the promoter. DNA sequence analysis revealed that each cap site was located at approximately 30 nucleotide (nt) downstream of three distinct TATA-like sequences. In primary cultures of rat granulosa cells, transfection studies using 5'-flanking regions of follistatin gene fused to the chloramphenicol acetyltransferase (CAT) reporter gene revealed the presence of two DNA segments that act to suppress basal transcriptional activity. The promoter activity of the CAT construct containing 2.6 kilo base pairs (kb) of 5'-flanking region was induced 2.5-fold above basal activity by forskolin (10 microM), and 1.6-fold by 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nM). Co-treatment with forskolin and TPA resulted in a 6.4-fold induction in its promoter activity, suggesting that two distinct signal transduction pathways, the cAMP-dependent protein kinase-A pathway and diacylglycerol-dependent protein kinase-C pathway, act coordinately to modulate follistatin gene transcription. Experiments using a series of 5'-flanking region deletion constructs located the regulatory regions responsive to these two pharmacological agents at nt -312 to -32 and -35 to +139.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0303-7207
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-109
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8472873-Activins, pubmed-meshheading:8472873-Amino Acid Sequence, pubmed-meshheading:8472873-Animals, pubmed-meshheading:8472873-Base Sequence, pubmed-meshheading:8472873-Cells, Cultured, pubmed-meshheading:8472873-Female, pubmed-meshheading:8472873-Follistatin, pubmed-meshheading:8472873-Forskolin, pubmed-meshheading:8472873-Gene Expression Regulation, pubmed-meshheading:8472873-Genes, pubmed-meshheading:8472873-Genes, Synthetic, pubmed-meshheading:8472873-Glycoproteins, pubmed-meshheading:8472873-Granulosa Cells, pubmed-meshheading:8472873-Inhibins, pubmed-meshheading:8472873-Molecular Sequence Data, pubmed-meshheading:8472873-Promoter Regions, Genetic, pubmed-meshheading:8472873-RNA Caps, pubmed-meshheading:8472873-Rats, pubmed-meshheading:8472873-Rats, Sprague-Dawley, pubmed-meshheading:8472873-Recombinant Fusion Proteins, pubmed-meshheading:8472873-Tetradecanoylphorbol Acetate
pubmed:year
1993
pubmed:articleTitle
Structural and functional characterization of the rat follistatin (activin-binding protein) gene promoter.
pubmed:affiliation
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.