Regulation of gene expression by B cell specific transcription factors / Fang Zhao.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Zhao, Fang.

Contributor:

Kadesch, Tom, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Allergy and Immunology.

Academic Dissertations as Topic.

Medical Subjects:

Allergy and Immunology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Physical Description:

xiv, 194 pages : illustrations ; 29 cm

Production:

2002.

Summary:

The development of B cells is regulated by B cell specific genes, whose tissue specific and differentiation stage specific expression dependents on the combinatorial effects of many transcription factors. Therefore, it is important to characterize the interplay among these transcription factors in order to understand the highly regulated B cell differentiation program.

In this thesis, I studied the combinatorial effects of some transcription factors on the expression of a subset of B cell specific genes. I observed dual function of EBF in transcriptional regulation. It activated lambda5 gene transcription as previously reported and inhibited E47 mediated activation of the Emu enhancer. Such inhibition did not involve EBF DNA binding. Instead, EBF appeared to function by interacting with p300/CBP and inhibiting its HAT activity. Furthermore, transcriptional activation by EBF did not involve p300/CBP, since EBF and CBP could not bind DNA at the same time and activation of the lambda5 promoter by EBF was not sensitive to E1a. By contrast, E1a inhibited the transcriptional synergy of EBF and E47 on lambda5 imparted by E47, a protein known to recruit p300/CBP but unable to activate lambda5 expression in the absence of EBF. Finally, I showed that EBF interacted with BRG1, a component of the SWI/SNF complex. Based on the above studies, I have proposed a model in which EBF binds to and represses the HAT activity of p300/CBP until it binds to target promoters. For one such promoter, lambda5, the synergy between EBF and E47 occurs due to a collaboration between SWI/SNF recruited by EBF and p300/CBP recruited by E47.

I also carried out collaborative experiments aimed at identifying target genes of the E2A proteins. Using an inducible system, I demonstrated that E2A can promote cell cycle progression in both NIH 3T3 and B cells. Their downstream targets include several cell cycle genes such as cyclins A and D. This study may help us to better understand the functions of E2A in B cell development as well as other developmental processes.

Notes:

Adviser: Tom Kadesch.

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2002.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3073081.

OCLC:

244972901