MECHANISMS OF EPIGENETIC REGULATION IN EARLY CELL FATE DETERMINATION

早期细胞命运决定的表观遗传调控机制

• 批准号: 8363801
• 负责人: Joanna Wysocka
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363801
• 关键词: Binding; Biological; Blood; Blood Cells; Cells; Child; Childhood Leukemia; Cues; DNA Sequence; Development; Drug Delivery Systems; Drug resistance; Enzymes; Epigenetic Process; Funding; Gene Expression; Genes; Genetic; Grant; Histones; Human body; Maps; Mass Spectrum Analysis; Muscle; Myeloid-Lymphoid Leukemia Protein; National Center for Research Resources; Oncogenes; Pathogenesis; Play; Principal Investigator; Process; Regulation; Research; Research Infrastructure; Resources; Role; Skin; Source; Stem cells; Time; United States National Institutes of Health; Writing; cancer cell; cell type; cost; embryonic stem cell; histone methyltransferase; improved; leukemia; programs; stem; tandem mass spectrometry; zygote

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The human body is made of hundreds of specialized cell forms ranging from skin, muscle to blood. All of these cells arise from a single ancestor (i.e. the zygote) and share the same genetic information. How specialized cell types are programmed and maintained during development, in a way that does not involve changes in DNA sequence, is a profound biological question. The mixed-lineage leukemia (MLL) proteins, which are histone methyltransferase enzymes, play a critical role in cell fate determination and pathogenesis of a drug-resistant form of childhood leukemia (mixed-lineage leukemia, MLL). MLL proteins turn on specific sets of genes by "writing" methyl marks at histones, transforming stem or progenitor cells to lineage specific cells. In children with mixed-lineage leukemia, MLL proteins are misregulated, which causes under expression of genes important for early development of blood cells and over expression of genes that transform blood progenitor cells to leukemia cancer cells. How inter- or intracellular circuitry or environmental cues interact with MLL proteins to precisely target MLL to the right genes in space and time is poorly studied. To gain understanding, we plan to determine the dynamic binding partners of MLL during the process of ES differentiation using tandem mass spectrometry. If successful, this research will generate a dynamic interactome map of MLL proteins in ES cells and during differentiation, which will not only advance our understanding of cell fate determination, but also provide possible drug targets that will improve treatment of MLL.

这个子项目是利用这些资源的众多研究子项目之一