Abstract

The human beta-globin locus control region (LCR) is a powerful chromosome organizational and regulatory entity and is required for both chromatin remodeling as well as for optimal expression of globin genes during erythroid development. Dr. Bungert has recently shown through analysis of germ line YAC-transformed transgenic animals that the dominant regulatory domain controlling the activity of all of the human beta-locus genes (LCR) throughout development is a single functional genetic entity. In the first specific aim, he proposes to analyze individual hypersensitive site mutations within the human beta-globin LCR and to examine the consequences of these mutations on human beta-globin locus gene activation after the mutant YACs are incorporated into germ line transgenic mice. In the second specific aim, he proposes to initiate a detailed structure/function analysis of the active LCR.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052356-05
Application #
6177888
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
1997-06-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
5
Fiscal Year
2000
Total Cost
$130,050
Indirect Cost

  Institution

Name
University of Florida
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Li, Biaoru; Zhu, Xingguo; Hossain, Mir A et al. (2018) Fetal hemoglobin induction in sickle erythroid progenitors using a synthetic zinc finger DNA-binding domain. Haematologica 103:e384-e387
Shen, Yong; Nar, Rukiye; Fan, Alex X et al. (2018) Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci. J Cell Biochem 119:712-722
Hossain, Mir A; Knudson, Isaac J; Thakur, Shaleen et al. (2017) Engineered Zinc Finger DNA-Binding Domains: Synthesis, Assessment of DNA-Binding Affinity, and Direct Protein Delivery to Mammalian Cells. Methods Mol Biol 1654:361-375
Hossain, Mir A; Bungert, Jörg (2017) Genome Editing for Sickle Cell Disease: A Little BCL11A Goes a Long Way. Mol Ther 25:561-562
Hossain, Mir A; Shen, Yong; Knudson, Isaac et al. (2016) Activation of Fetal ?-globin Gene Expression via Direct Protein Delivery of Synthetic Zinc-finger DNA-Binding Domains. Mol Ther Nucleic Acids 5:e378
Hossain, Mir A; Shen, Yong; Knudson, Isaac et al. (2016) Activation of Fetal ?-globin Gene Expression via Direct Protein Delivery of Synthetic Zinc-finger DNA-Binding Domains. Mol Ther Nucleic Acids 5:e378
Deng, Changwang; Li, Ying; Zhou, Lei et al. (2016) HoxBlinc RNA Recruits Set1/MLL Complexes to Activate Hox Gene Expression Patterns and Mesoderm Lineage Development. Cell Rep 14:103-114
Stees, Jared R; Hossain, Mir A; Sunose, Tomoki et al. (2016) High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range ?-Globin Gene Regulation. Mol Cell Biol 36:238-50
Li, Ying; Schulz, Vincent P; Deng, Changwang et al. (2016) Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic Acids Res 44:7173-88
Hossain, Mir A; Barrow, Joeva J; Shen, Yong et al. (2015) Artificial zinc finger DNA binding domains: versatile tools for genome engineering and modulation of gene expression. J Cell Biochem 116:2435-44

Showing the most recent 10 out of 27 publications