Hematopoiesis is controlled by an intricate network of gene transcription factors, to ensure the development and maintenance of all types of blood cells in vertebrates. Dysfunction of many of the transcription factors necessary for hematopoiesis is associated with different types of leukemias as well as congenital cytopenias. The long term objective of this proposal is to identify the mechanisms by which the zinc finger X-linked duplicated C (ZXDC) gene affects myelopoiesis. One ZXD family member, ZXDC, interacts with at least two key transcription factors in myeloid cell development: PU.1 and Gfi1. Using models of myeloid differentiation, ZXDC was found to participate in eosinophil development and may also have a role in maintaining progenitor status. This pilot project has two goals: (1) characterize the role of ZXDC in myelopoiesis employing human primary cells and (2) identify putative ZXDC target genes by an integrated genomic screen employing expression profiling and chromatin immunoprecipitation followed by microarray (ChIP- chip). These data will expand the gene regulatory network controlling myeloid cell development, identify genes regulated by ZXDC involved in this process and provide the foundation for a comprehensive mechanistic analysis of ZXDC function in hematopoiesis.
The mechanisms that control the development of the many types of blood cells in humans are complex. When these mechanisms function incorrectly, they can contribute to the development of leukemia. The proposed research is to characterize the mechanisms by which a newly identified family of proteins, the transcription factor family ZXD, affects the development of blood cells.
|Ramsey, Jon E; Fontes, Joseph D (2013) The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression. Mol Immunol 56:768-80|