The influence of the ZXDC protein on myelopoiesis

描述（由申请人提供）：造血是由一个复杂的基因转录因子网络控制的，以确保脊椎动物所有类型血细胞的发育和维持。许多造血所必需的转录因子的功能障碍与不同类型的白血病以及先天性细胞减少症有关。本研究的长期目标是确定锌指x连锁重复C （ZXDC）基因影响骨髓生成的机制。ZXD家族的一个成员，ZXDC，在髓细胞发育中至少与两个关键转录因子相互作用：PU.1和Gfi1。通过骨髓分化模型，ZXDC被发现参与嗜酸性粒细胞的发育，并可能在维持祖细胞状态中发挥作用。该试点项目有两个目标：(1)利用人原代细胞表征ZXDC在骨髓形成中的作用；(2)利用表达谱和染色质免疫沉淀以及微阵列（ChIP- ChIP）技术，通过集成基因组筛选鉴定可能的ZXDC靶基因。这些数据将扩展髓细胞发育的基因调控网络，识别ZXDC调控的参与该过程的基因，为全面分析ZXDC在造血功能中的作用机制提供基础。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.