Functions of transcription factor Oct -2 in immunoglobulin-secreting cells.
Item
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Title
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Functions of transcription factor Oct -2 in immunoglobulin-secreting cells.
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Identifier
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AAI9986375
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identifier
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9986375
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Creator
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Sharif, Mubaraka Nusrat.
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Contributor
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Adviser: Laurel Eckhardt
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Date
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2000
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular
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Abstract
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Oct-1 and Oct-2 belong to the POU homeodomain family of transcription factors that bind the conserved octamer motif---a key regulatory element found in all Ig promoters as well as in immunoglobulin gene enhancers. Oct-1 expression is virtually ubiquitous, implicated in control of genes expressed by all cells, while Oct-2 is predominantly B lineage-restricted. Both Oct-1 and Oct-2 can functionally interact through their POU domains with a B cell-restricted co-activator called OBF-1/BOB-1/OCA-B to mediate strong immunoglobulin promoter activity. Since both Oct-1 and Oct-2 can mediate Ig promoter activity in B cells, there has been some question as to whether these two octamer binding factors serve distinct function in lymphocytes.;We have used the approach of somatic cell fusion to explore the functional differences between the two octamer binding factors. Previous studies in our lab have demonstrated that at the immunoglobulin secreting stage of B cell development, Oct-2 plays a critical role in regulating the expression of several B cell-specific genes. The pronounced effect of Oct-2 on the phenotype of plasmacytoma x T lymphoma hybrids established a unique role for this transcription factor in regulating the genetic program of an Ig-secreting cell.;In the studies presented in this thesis, we have exploited the functional differences between the two octamer binding transcription factors using chimeric hOct-1/hOct-2 proteins in our cell fusion experiments. Our findings further demonstrate a unique function for Oct-2 in Ig secreting cells, and show that this function (rescue of Ig and other B cell-specific genes), cannot be achieved by Oct-1, the other octamer binding factor. Our findings thus provide evidence that the C-terminal domain of Oct-2 is critical for the unique functions of Oct-2 in Ig-secreting cells.;Studies in our lab and others have suggested that a tissue-restricted co-factor interacts with the C-terminal domain of Oct-2 to mediate Oct-2 function. We have used yeast two-hybrid approach to identify proteins that can interact with this region of Oct-2. Preliminary results of our screens are also described in this thesis.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
