Characterization of CTIP1 in Immune Cells

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DESCRIPTION (provided by applicant): Hematopoiesis and cellular immunity are complex processes controlled by growth factors, cellular interactions, and regulated gene expression. We have recently identified a novel transcription factor which is expressed in the immune system and circumstantial evidence suggests a role for this protein in the development and function of immune cells. COUP TF-Interacting Protein 1 (CTIP1) is a member of a novel family of C2H2 zinc finger proteins that have recently been demonstrated to function as modulators of gene transcription. CTIP1 regulates transcription by physically interacting with Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP TF) orphan nuclear receptors, or by directly binding to consensus CTIP response elements. CTIP1 is highly expressed in murine bone marrow, spleen, lymph nodes, and purified B-cells and dendritic cells. The goal of this study is to test the hypothesis that CTIP1 plays a role in the development and function of immune cells. The aims of the proposed research are: (1) to characterize the expression of CTIP1 in developing immune cells: (2) to elucidate possible functions of CTIP1 in leukocytes: and (3) to identify target genes that are regulated by CTIP1. Defining the function of this protein is of great biomedical interest not only because of its role as a bona fide transcription factor but also because this gene was recently identified as a site of retroviral insertion that results in cellular transformation and leukemogenesis. Upon the successful completion of this proposal, our expectation is that these studies will advance our knowledge of hematopoiesis and immune cell regulation and further elucidate the molecular and cellular functions of CTIP1.