Functional hierarchy of tissue -specific transcription factors in immunoglobulin -secreting cells.
Item
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Title
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Functional hierarchy of tissue -specific transcription factors in immunoglobulin -secreting cells.
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Identifier
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AAI3063878
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identifier
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3063878
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Creator
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Salas, Mabel.
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Contributor
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Adviser: Laurel Eckhardt
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Date
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2002
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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 | Health Sciences, Immunology
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Abstract
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B and T lymphocytes arise from a common precursor in the bone marrow but ultimately acquire very different functions. The difference in function is largely attributable to the expression of tissue-specific transcription factors that activate discrete sets of genes. B cells express several tissue-specific transcription factors that bind to enhancer and promoter elements within the immunoglobulin (Ig) and other tissue-restricted genes, activating the B cell program. When an Ig-secreting cell is fused to a T lymphoma, however, genes encoding both tissue-specific transcription factors and tissue-specific structural genes (e.g. Oct-2, PU.1, OCA-B, Ig heavy and light chain and J chain) are extinguished at the transcriptional level. We have previously shown that all tested tissue-specific genes of the Ig-secreting cell are rescued from silencing when Oct-2 expression is artificially expressed. This suggested that the transcription factor Oct-2 plays a central role in maintaining the genetic program of these cells. We have further investigated the role of two other factors that are expressed in the Ig-secreting cell but not in the T lymphoma. One of these factors is the B cell and macrophage-specific transcription factor, PU.1, and the other is the coactivator of octamer-binding factors, OCA-B. Our results have shown that PU.1 cannot rescue any of the tested B cell genes or reciprocally regulate Oct-2's function. Surprisingly, OCA-B rescues all tissue-specific and structural genes, can reciprocally regulate Oct-2 and it is the exclusive partner of Oct-2 in rescuing the plasmacyte-specific program. In conclusion, transcription factor PU.1 plays a subordinate role to that of Oct-2 and coactivator OCA-B and Oct-2 are at the highest level of the hierarchy in the Ig-secreting cell.
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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.
