and specific aims): The investigators have recently isolated a lung transcription factor, LKLF-1, which belongs to the Kruppel family of transcription factors. Because LKLF-1, is one of the few transcription factors expressed almost exclusively in the lung, studies have been initiated to understand its role in lung specific gene expression and development. In situ analysis of adult lung indicates that it is expressed in epithelial cells including both Clara and type II cells, however, Northern blot analysis also shows that LKLF-1 is expressed in embryos before lung development is apparent and thus this gene may also play an important role in development. Mice lacking LKLF-1 display embryonic lethal phenotype. The LKLF-1 gene thus represents a transcription factor which is undoubtly involved in gene regulation in adult lung but is also critical in other systems during embryonic development.
The specific aims are: 1) to carry out detailed analysis of tissue specific and developmental expression of the LKLF-1 gene using in situ and whole mount hybridization analysis; 2) to further characterize the defect resulting from the lack of LKLF-1 expression in our knockout mice utilizing double knockout ES cells to form chimeric animals, organ cultures and analysis of in vitro hematopoiesis; 3) to characterize the DNA binding and activation domains of LKLF-1; 4) to describe the regulation of the LKLF-1 gene particularly in lung epithelial cells; and 5) to determine the chromosomal location of the mouse and human LKLF-1 genes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057281-04
Application #
6184248
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1997-08-08
Project End
2001-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
2000
Total Cost
$284,599
Indirect Cost
Name
University of Cincinnati
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Pei, Liming; Leblanc, Mathias; Barish, Grant et al. (2011) Thyroid hormone receptor repression is linked to type I pneumocyte-associated respiratory distress syndrome. Nat Med 17:1466-72
Wu, Jinghai; Bohanan, Cynthia S; Neumann, Jon C et al. (2008) KLF2 transcription factor modulates blood vessel maturation through smooth muscle cell migration. J Biol Chem 283:3942-50
Huddleson, Justin P; Ahmad, Nisar; Lingrel, Jerry B (2006) Up-regulation of the KLF2 transcription factor by fluid shear stress requires nucleolin. J Biol Chem 281:15121-8
Ahmad, Nisar; Lingrel, Jerry B (2005) Kruppel-like factor 2 transcriptional regulation involves heterogeneous nuclear ribonucleoproteins and acetyltransferases. Biochemistry 44:6276-85
Wu, Jinghai; Srinivasan, Seetha V; Neumann, Jon C et al. (2005) The KLF2 transcription factor does not affect the formation of preadipocytes but inhibits their differentiation into adipocytes. Biochemistry 44:11098-105
Huddleson, Justin P; Ahmad, Nisar; Srinivasan, Seetha et al. (2005) Induction of KLF2 by fluid shear stress requires a novel promoter element activated by a phosphatidylinositol 3-kinase-dependent chromatin-remodeling pathway. J Biol Chem 280:23371-9
Wu, Jinghai; Lingrel, Jerry B (2005) Kruppel-like factor 2, a novel immediate-early transcriptional factor, regulates IL-2 expression in T lymphocyte activation. J Immunol 175:3060-6
Huddleson, Justin P; Srinivasan, Seetha; Ahmad, Nisar et al. (2004) Fluid shear stress induces endothelial KLF2 gene expression through a defined promoter region. Biol Chem 385:723-9
Wu, Jinghai; Lingrel, Jerry B (2004) KLF2 inhibits Jurkat T leukemia cell growth via upregulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1. Oncogene 23:8088-96
Zhang, Xiaoling; Srinivasan, Seetha V; Lingrel, Jerry B (2004) WWP1-dependent ubiquitination and degradation of the lung Kruppel-like factor, KLF2. Biochem Biophys Res Commun 316:139-48

Showing the most recent 10 out of 15 publications