Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis Academic Article uri icon

Overview

MeSH Major

  • DNA Methylation
  • Erythroid Cells
  • Erythropoiesis
  • Regulatory Sequences, Nucleic Acid

abstract

  • Hematopoietic stem cell differentiation involves the silencing of self-renewal genes and induction of a specific transcriptional program. Identification of multiple covalent cytosine modifications raises the question of how these derivatized bases influence stem cell commitment. Using a replicative primary human hematopoietic stem/progenitor cell differentiation system, we demonstrate dynamic changes of 5-hydroxymethylcytosine (5-hmC) during stem cell commitment and differentiation to the erythroid lineage. Genomic loci that maintain or gain 5-hmC density throughout erythroid differentiation contain binding sites for erythroid transcription factors and several factors not previously recognized as erythroid-specific factors. The functional importance of 5-hmC was demonstrated by impaired erythroid differentiation, with augmentation of myeloid potential, and disrupted 5-hmC patterning in leukemia patient-derived CD34+ stem/early progenitor cells with TET methylcytosine dioxygenase 2 (TET2) mutations. Thus, chemical conjugation and affinity purification of 5-hmC-enriched sequences followed by sequencing serve as resources for deciphering functional implications for gene expression during stem cell commitment and differentiation along a particular lineage.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3976649

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2013.11.044

PubMed ID

  • 24373966

Additional Document Info

start page

  • 231

end page

  • 44

volume

  • 6

number

  • 1