Genomics

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Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE19502 | GEO | 2010/03/01

SECONDARY ACCESSION(S): PRJNA122423

REPOSITORIES: GEO

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