scholarly journals Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2230-2240 ◽  
Author(s):  
Satyanaryana Eleswarapu ◽  
Zhiliang Gu ◽  
Honglin Jiang
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Binding Sites ◽  
Mouse Liver ◽  
Consensus Sequence ◽  
Reporter Gene Expression ◽  
Hormone Regulation ◽  
Signal Transducer ◽  
Igf I ◽  
I Gene

The transcription factor signal transducer and activator of transcription (STAT)-5 mediates GH stimulation of IGF-I gene expression in the liver. Previous studies suggested that STAT5 might exert this effect by binding to an IGF-I intron 2 region and a distal 5′-flanking region each containing two STAT5 binding sites. Here we report the identification of three additional chromosomal regions containing a total of five putative STAT5 binding sites that may mediate GH-induced STAT5 activation of IGF-I gene expression in the mouse liver. By comparing an 170-kb mouse genomic DNA containing the IGF-I gene with the corresponding human sequence, we identified 19 putative STAT5 binding sites that bear the consensus sequence of STAT5 binding site and are conserved across the two species. Chromatin immunoprecipitation assays indicated that five chromosomal regions containing a total of nine of the 19 putative STAT5 binding sites were bound by STAT5 in the mouse liver in response to GH administration and that these bindings preceded or coincided with GH-increased IGF-I gene transcription. Two of the five chromosomal regions correspond to those previously identified in other species, and the three new chromosomal regions that contain a total of five putative STAT5 binding sites are IGF-I intron 3 regions located at least 26 kb from the transcription start site. Gel-shift assays confirmed the binding of the five new putative STAT5 binding sites as well as three of the four previously identified STAT5 binding sites to GH-activated STAT5 from the mouse liver. Cotransfection analyses indicated that, although each of the five chromosomal regions was able to mediate STAT5 activation of reporter gene expression, together they mediated greater STAT5 activation of reporter gene expression in response to GH. Overall, these results suggest that GH-induced STAT5 activation of IGF-I gene expression in the mouse liver might be collectively mediated by at least eight STAT5 binding sites located in distal intronic and 5′-flanking regions of the IGF-I gene.

scholarly journals Multiple Distant STAT5 Binding Sites Mediate Growth Hormone Regulation of IGF‐I Gene Expression

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Honglin Jiang ◽  
Satyanaryana Eleswarapu ◽  
Zhiliang Gu ◽  
Ying Wang ◽  
Bettina Heid
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Binding Sites ◽  
Hormone Regulation ◽  
Igf I ◽  
I Gene

decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3695-3702 ◽  
Author(s):  
X. Yang ◽  
M. van Beest ◽  
H. Clevers ◽  
T. Jones ◽  
D.A. Hursh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Transforming Growth Factor ◽  
Ectopic Expression ◽  
Reporter Gene Expression ◽  
Enhancer Element ◽  
Visceral Mesoderm

Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.

scholarly journals Cell Signaling Switches HOX-PBX Complexes from Repressors to Activators of Transcription Mediated by Histone Deacetylases and Histone Acetyltransferases

2000 ◽  
Vol 20 (22) ◽  
pp. 8623-8633 ◽  
Author(s):  
Maya Saleh ◽  
Isabel Rambaldi ◽  
Xiang-Jiao Yang ◽  
Mark S. Featherstone
Keyword(s):  
Gene Expression ◽  
Cell Signaling ◽  
Reporter Gene ◽  
Binding Sites ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Cell Aggregation ◽  
Reporter Gene Expression ◽  
Hek293 Cells ◽  
Creb Binding Protein

ABSTRACT The Hoxb1 autoregulatory element comprises three HOX-PBX binding sites. Despite the presence of HOXB1 and PBX1, this enhancer fails to activate reporter gene expression in retinoic acid-treated P19 cell monolayers. Activation requires cell aggregation in addition to RA. This suggests that HOX-PBX complexes may repress transcription under some conditions. Consistent with this, multimerized HOX-PBX binding sites repress reporter gene expression in HEK293 cells. We provide a mechanistic basis for repressor function by demonstrating that a corepressor complex, including histone deacetylases (HDACs) 1 and 3, mSIN3B, and N-CoR/SMRT, interacts with PBX1A. We map a site of interaction with HDAC1 to the PBX1 N terminus and show that the PBX partner is required for repression by the HOX-PBX complex. Treatment with the deacetylase inhibitor trichostatin A not only relieves repression but also converts the HOX-PBX complex to a net activator of transcription. We show that this activation function is mediated by the recruitment of the coactivator CREB-binding protein by the HOX partner. Interestingly, HOX-PBX complexes are switched from transcriptional repressors to activators in response to protein kinase A signaling or cell aggregation. Together, our results suggest a model whereby the HOX-PBX complex can act as a repressor or activator of transcription via association with corepressors and coactivators. The model implies that cell signaling is a direct determinant of HOX-PBX function in the patterning of the animal embryo.

Reporter Gene Expression in G2 of the 1-Cell Mouse Embryo

1993 ◽  
Vol 156 (2) ◽  
pp. 552-556 ◽  
Author(s):  
Prahlad T. Ram ◽  
Richard M. Schultz
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Mouse Embryo ◽  
Reporter Gene Expression ◽  
Cell Mouse Embryo

Tetracycline-regulated reporter gene expression in the moss Physcomitrella patens

1996 ◽  
Vol 30 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Mathias Zeidler ◽  
Christiane Gatz ◽  
Elmar Hartmann ◽  
Jon Hughes
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Physcomitrella Patens ◽  
Reporter Gene Expression

scholarly journals A 4kb Fragment of the Desmocollin 3 Promoter Directs Reporter Gene Expression to Parakeratotic Epidermis and Primary Hair Follicles

2007 ◽  
Vol 127 (1) ◽  
pp. 245-247 ◽  
Author(s):  
Anita J. Merritt ◽  
Kuichun Zhu ◽  
David R. Garrod ◽  
Martyn A.J. Chidgey
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Hair Follicles ◽  
Reporter Gene Expression

Regulation of insulin-like growth factor-I gene expression by growth factors in cultured vascular smooth muscle cells

1990 ◽  
Vol 125 (3) ◽  
pp. 381-386 ◽  
Author(s):  
K. E. Bornfeldt ◽  
H. J. Arnqvist ◽  
G. Norstedt
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Basic Fgf ◽  
Aortic Smooth Muscle ◽  
Factor I ◽  
Igf I ◽  
I Gene

ABSTRACT The aim of this investigation was to study the regulation of insulin-like growth factor-I (IGF-I) gene expression in cultured rat aortic smooth muscle cells. Near-confluent cells were deprived of serum for 24 h and then exposed to IGF-I, insulin, serum, basic fibroblast growth factor (basic FGF), platelet-derived growth factor (PDGF-BB; consisting of B-chain homodimer) or GH for 24 h. Levels of IGF-I mRNA were measured by solution hybridization. The level of IGF-I mRNA was markedly decreased by 10% (v/v) newborn calf serum (78 ± 4 (s.e.m.) % decrease), 1 nmol basic FGF/1 (53 ± 8%), and 1 nmol PDGF-BB/1 (40 ± 3%) when measured after 24 h. The effect of PDGF-BB was significant after 6 h and became more marked after 24 h. GH (1 nmol/l or 0.1 μmol/l or insulin (1 nmol/l had no effect after 24 h, whereas IGF-I (1 nmol/l and insulin (10 μmol/l increased IGF-I mRNA 64 ± 20% and 46±14% respectively. The increase caused by IGF-I was demonstrated after 3 h, and was most marked after 24 h. Using Northern blot analysis of cultured aortic smooth muscle cells, IGF-I transcripts of 7-4, 1.7 and 1.1–0.8 kilobases were observed. Exposure of the cells to 10% serum, 1 nmol basic FGF/1 or 1 nmol PDGF-BB/1 for 48 h increased the cell number by 104 ±7%, 64 ± 3% and 61±22% respectively, while IGF-I, insulin and GH had little effect. In conclusion, IGF-I, and high concentrations of insulin, increased IGF-I mRNA in vascular smooth muscle cells, whereas factors which were stronger mitogens decreased IGF-I gene expression. Journal of Endocrinology (1990) 125, 381–386

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