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Transcription factor regulation of globin gene expression and strategy for gene therapy of sickle cell disease

Posted on:1997-03-03Degree:Ph.DType:Dissertation
University:The University of Alabama at BirminghamCandidate:Donze, DavidFull Text:PDF
GTID:1463390014983973Subject:Molecular biology
Abstract/Summary:
ukaryotic gene expression is predominantly regulated at the level of transcription. In humans, the high level, developmentally regulated, and tissue specific expression of hemoglobin genes is regulated by cis-acting sequences near the individual gene promoters and within a complex upstream element called the locus control region (LCR). Protein transcription factors that bind to these cis-acting sequences are critical for transcriptional regulation. We have identified a protein that binds to AP1-like sites within the LCR and have designated it LCR-F1. This protein is a member of a new family of regulatory factors that contain a 63 amino acid "CNC domain" overlapping the basic region. This domain is approximately 70% identical in the Drosophila Cap'N'Collar (CNC) protein, NF-E2 and LCR-F1. LCR-F1 activates transcription from transfected LCR-globin gene reporter constructs, specifically in erythroid cells, and may be a critical factor involved in human globin gene regulation.;Erythroid Kruppel-like factor (EKLF) is an erythroid specific zinc finger protein which binds to CACCC sequences. We have demonstrated that EKLF binds to the adult ;In humans, a second adult...
Keywords/Search Tags:Gene, Transcription, Expression, Protein, Factor, Regulation
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