The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells

Stem Cell Reports
Fabiana PernaStephen D Nimer

Abstract

Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development, and, thus, aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell populations, thereby affecting erythroid differentiation. Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia.

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Citations

Aug 26, 2015·Molecular and Cellular Biology·Felix LohmannJames J Bieker
Feb 23, 2020·Case Reports in Hematology·Anh Khoi VoHåkon Reikvam

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Methods Mentioned

BETA
flow cytometry
immunoprecipitation
ChIP
transfection
fluorescence-activated cell sorting
FACS
PCR

Software Mentioned

GSEA

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