The polycomb group protein L3MBTL1 repreßes a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • Chromosomal Proteins, Non-Histone
  • Gene Expression Regulation, Developmental
  • Hematopoiesis
  • Pluripotent Stem Cells
  • Smad5 Protein
  • Transcription, Genetic

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.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4400644

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2015.02.003

PubMed ID

  • 25754204

Additional Document Info

start page

  • 658

end page

  • 69

volume

  • 4

number

  • 4