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Role of GATA-1 in β-globin locus chromatin structure reorganization and eryrhoid [i.e. erythroid] gene expression.

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Call No.	Ph.D. 2004
Author	Layon, Michael E.
Title	Role of GATA-1 in β-globin locus chromatin structure reorganization and eryrhoid [i.e. erythroid] gene expression.
Date	2004
Abstract	Despite being cloned over twenty years ago, many regulatory mechanisms of the β-globin genes have yet to be fully elucidated. The regulation of the β-globin locus in erythroid cells requires chromatin structural changes before the genes can be expressed. Several cis -elements of the β-globin locus, known to be necessary for establishing erythroid-specific chromatin structures and gene expression have been characterized. Several trans -factors are also known to be required for this process, but their functions are not as well understood. Our research focuses on the zinc finger transcription factor GATA-1, which was originally discovered in cells of the erythroid lineage. To test the hypothesis that GATA-1 is sufficient to direct β-globin locus chromatin structure reorganization we studied GATA-1 expression in the human epithelial cell line HeLa S3. We then studied GATA-1's ability to regulate the expression of other factors known to be required for erythroid maturation.Expression of GATA-1 resulted in the formation of all four DNase I hypersensitive sites of the β-globin locus control region which are normally restricted to cells of erythroid lineage. In addition when GATA-1 was expressed in the non-erythroid cell line NAMALWA, the DNase I hypersensitive sites three and four formed. Expression of GATA-1 in the HeLa S3 cells resulted in transcription of several factors known to cooperate with GATA-1 during erythroid differentiation. While the mRNA for these genes were detected, we were unable to detect protein as measured by western analyses.
Description	ix, 125 leaves : ill. 28 cm.
Format	application/pdf
Advisor	Christopher H. Lowrey.
Subject	Chromatin -- Structure. Globin genes -- Expression. Transcription factors. Erythropoiesis. Genetic transcription -- Regulation.
College	Dartmouth Medical School -- Department of Pharmacology and Toxicology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.55

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	ROLE OF GATA-1 IN –GLOBIN LOCUS CHROMATIN STRUCTURE REORGANIZATION AND ERYRHOID GENE EXPRESSION A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Pharmacology and Toxicology By Michael E. Layon Jr. DARTMOUTH COLLEGE Hanover, New Hampshire May 11th 2004 Examining Committee _________________________ (Chair)Christopher H. Lowrey, M.D. _________________________ Joshua Hamilton, Ph.D. _________________________ Jacqueline Sinclair, Ph.D. _________________________ _________________________ Carol Folt, Ph.D. Nancy Speck, Ph.D.

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Role of GATA-1 in β-globin locus chromatin structure reorganization and eryrhoid [i.e. erythroid] gene expression.

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