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题目:: Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
ID:
状态:: 发布时间March 7, 2010 , 更新时间 May 1, 2014 , 提交时间 Dec. 15, 2009,
物种:: Mus musculus
摘要:: Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was instructive of HSC quiescence and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in stability of c-Myc protein regulated the HSC “gene expression signature”. Using whole genome genomic approaches, we identified specific regulators of HSC function that are directly controlled by c-Myc binding, however adult HSCs and embryonic stem cells sense and interpret distinctly c-Myc regulated gene expression. These studies show a ubiquitin ligase–substrate pair can orchestrate the molecular program of HSC differentiation. Gene expression profiles from c-Myc-High and c-Myc-Low expressing Lineage negative, c-Kit and Sca1 positive (LSKs) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by chromatin immunoprecipitation experiments.
实验种类:: transcription profiling by array
样本量:: 4
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数据号:: E-GEOD-19502, GSE19502
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