We propose to continue to study the regulation of differential gene expression using the model of avian red blood cell development. We are studying and have characterized (or are in the process of characterizing) 14 different erythroid-specific genes, and have generated antibody reagents for most of these. Furthermore, we have been able to directly demonstrate erythroid-specific control of two of these genes (beta-globin and histone H5) after transfection into precursor erythroid cells, and that the contol is elicited in beta-globin in a temporally-specific manner during erythropoiesis. During the term of this proposal, we wish to study the regulatory mechanism which confer the temporal-, abundance- and tissue- specificity of these genes by mutational analysis and by correlation of these findings on in vivo expression (both by translient assay and using a retrovirus vector) with the specific cis-acting sequences and the regulatory molecules, we will study the interaction of the regulatory proteins with their cognate gene-specific sequences in vitro. The model system examined in detail in this proposal is concerned with attempts to precisely delimit the cis-acting regulatory sequences making up the beta-globin enhancer, and, if possible, to separately define the sequences responsible for biochemical methods. Using the results of those studies, we plan to isolate the beta-globin regulatory molecule(s), and then clone those regulatory genes as a prelude to studying the interaction of purfied tissue-specific transcription factors with other erythroid- specific genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM028896-04A1
Application #
3276236
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1983-03-01
Project End
1991-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60208
Moriguchi, Takashi; Yu, Lei; Otsuki, Akihito et al. (2016) Gata3 Hypomorphic Mutant Mice Rescued with a Yeast Artificial Chromosome Transgene Suffer a Glomerular Mesangial Cell Defect. Mol Cell Biol 36:2272-81
Udager, Aaron M; Prakash, Ajay; Saenz, David A et al. (2014) Proper development of the outer longitudinal smooth muscle of the mouse pylorus requires Nkx2-5 and Gata3. Gastroenterology 146:157-165.e10
Lim, Kim-Chew; Hosoya, Tomonori; Brandt, William et al. (2012) Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. J Clin Invest 122:3705-17
Ku, Chia-Jui; Hosoya, Tomonori; Maillard, Ivan et al. (2012) GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry. Blood 119:2242-51
Hosoya-Ohmura, Sakie; Lin, Yu-Hsuan; Herrmann, Mary et al. (2011) An NK and T cell enhancer lies 280 kilobase pairs 3' to the gata3 structural gene. Mol Cell Biol 31:1894-904
Duncan, Jeremy S; Lim, Kim-Chew; Engel, James D et al. (2011) Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3. Int J Dev Biol 55:297-303
Hosoya, Tomonori; Maillard, Ivan; Engel, James D (2010) From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol Rev 238:110-25
Maeda, Atsuko; Moriguchi, Takashi; Hamada, Michito et al. (2009) Transcription factor GATA-3 is essential for lens development. Dev Dyn 238:2280-91
Hosoya, Tomonori; Kuroha, Takashi; Moriguchi, Takashi et al. (2009) GATA-3 is required for early T lineage progenitor development. J Exp Med 206:2987-3000
Hoshino, Tomofumi; Shimizu, Ritsuko; Ohmori, Shinya et al. (2008) Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT. Genes Cells 13:159-70

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