Control of megakaryocyte-specific gene regulation : GATA-1, FOG-1, FLI-1 cooperativity in alpha IIB gene expression / Xun Wang.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Wang, Xun.

Contributor:

Poncz, Mortimer, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Biochemistry and molecular biophysics.

Biochemistry and molecular biophysics--Penn dissertations.

Biochemistry and Molecular Biophysics.

Academic Dissertations as Topic.

Medical Subjects:

Biochemistry and Molecular Biophysics.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Biochemistry and molecular biophysics.

Biochemistry and molecular biophysics--Penn dissertations.

Physical Description:

x, 139 pages : illustrations ; 29 cm

Production:

2003.

Summary:

The transcription factor GATA-1 and its cofactor FOG-1 are essential for the normal development of erythroid cells and megakaryocytes. FOG-1 can stimulate or inhibit GATA-1 activity depending on cell and promoter context. However, the mechanism(s) by which GATA-1 interacts with FOG-1 to regulate the expression of distinct sets of genes in megakaryocytes and erythroid cells is not well understood. The alphaIIb gene, which encodes the a integrin chain of the platelet-specific fibrinogen receptor alphaIIb/beta3, has long served as a model for understanding the molecular basis of high level, megakaryocyte-specific gene expression. In this thesis, I examined the molecular basis for the megakaryocytes-restricted activation of alphaIIb gene by GATA-1 and FOG-1, providing new insights into a GATA-Ets signature motif found in the promoter regions of alphaIIb gene and other numerous megakaryocytic genes. In addition, I identified Fli-1 as a tissue-specific Ets binding protein that converts FOG-1 from a repressor into a GATA-1 coactivator. The implication of these findings might extend beyond megakaryocyte regulation to the regulation of genes controlled by GATA and FOG proteins in diverse tissues, including erythroid cells, lymphoid cells and the heart.

Notes:

Supervisor: Mortimer Poncz.

Thesis (Ph.D. in Biochemistry and Molecular Biophysics) -- University of Pennsylvania, 2003.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3087477.

OCLC:

244971712