Abstract

The applicant proposes to investigate the hypothesis that multiple GH-regulated signaling pathways interact at various levels into networks which lead to specific responses to GH. These interactions occur at the level of transcription factors and their binding, as well as by crosstalk among more proximal signaling molecular between the GH receptor and the nucleus. To examine this hypothesis the applicant plans to analyze transcriptional regulation of the c-fos gene by GH.
Four Specific Aims are proposed: (1) To define interactions among GH-regulated DNA-protein complexes associated with the c-fos gene; (2) To identify interactions among GH-responsive DNA sequences by analysis of DNA-binding proteins; (3) To examine regulation by GH of DNA-binding complexes; (4) To determine how interactions in DNA-protein complexes contribute to specificity in GH versus cytokine regulation of c-fos transcription.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046072-02
Application #
2444080
Study Section
Endocrinology Study Section (END)
Program Officer
Sato, Sheryl M
Project Start
1996-09-30
Project End
2000-06-30
Budget Start
1997-08-10
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Carter-Su, Christin; Schwartz, Jessica; Argetsinger, Lawrence S (2016) Growth hormone signaling pathways. Growth Horm IGF Res 28:11-5
LaPensee, Christopher R; Lin, Grace; Dent, Alexander L et al. (2014) Deficiency of the transcriptional repressor B cell lymphoma 6 (Bcl6) is accompanied by dysregulated lipid metabolism. PLoS One 9:e97090
Lin, Grace; LaPensee, Christopher R; Qin, Zhaohui S et al. (2014) Reciprocal occupancy of BCL6 and STAT5 on Growth Hormone target genes: contrasting transcriptional outcomes and promoter-specific roles of p300 and HDAC3. Mol Cell Endocrinol 395:19-31
Cui, Tracy X; Lin, Grace; LaPensee, Christopher R et al. (2011) C/EBP? mediates growth hormone-regulated expression of multiple target genes. Mol Endocrinol 25:681-93
Chen, Yili; Lin, Grace; Huo, Jeffrey S et al. (2009) Computational and functional analysis of growth hormone (GH)-regulated genes identifies the transcriptional repressor B-cell lymphoma 6 (Bc16) as a participant in GH-regulated transcription. Endocrinology 150:3645-54
Cesena, Teresa I; Cui, Tracy X; Subramanian, Lalitha et al. (2008) Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta at K39 in mediating gene transcription. Mol Cell Endocrinol 289:94-101
Cui, Tracy Xiao; Kwok, Roland; Schwartz, Jessica (2008) Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein beta in GH-stimulated c-fos expression. J Endocrinol 196:89-100
Cesena, Teresa I; Cui, Tracy Xiao; Piwien-Pilipuk, Graciela et al. (2007) Multiple mechanisms of growth hormone-regulated gene transcription. Mol Genet Metab 90:126-33
Cesena, Teresa I; Cardinaux, Jean-Rene; Kwok, Roland et al. (2007) CCAAT/enhancer-binding protein (C/EBP) beta is acetylated at multiple lysines: acetylation of C/EBPbeta at lysine 39 modulates its ability to activate transcription. J Biol Chem 282:956-67
Huo, Jeffrey S; McEachin, Richard C; Cui, Tracy Xiao et al. (2006) Profiles of growth hormone (GH)-regulated genes reveal time-dependent responses and identify a mechanism for regulation of activating transcription factor 3 by GH. J Biol Chem 281:4132-41

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