High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis

Blood. 2014 Apr 24;123(17):e46-57. doi: 10.1182/blood-2013-02-483537. Epub 2014 Mar 26.

Abstract

Hematopoietic differentiation is governed by a complex regulatory program controlling the generation of different lineages of blood cells from multipotent hematopoietic stem cells. The transcriptional program that dictates hematopoietic cell fate and differentiation requires an epigenetic memory function provided by a network of epigenetic factors regulating DNA methylation, posttranslational histone modifications, and chromatin structure. Aberrant interactions between epigenetic factors and transcription factors cause perturbations in the blood cell differentiation program that result in various types of hematopoietic disorders. To elucidate the contributions of different epigenetic factors in human hematopoiesis, high-throughput cap analysis of gene expression was used to build transcription profiles of 199 epigenetic factors in a wide range of blood cells. Our epigenetic transcriptome analysis revealed cell type- (eg, HELLS and ACTL6A), lineage- (eg, MLL), and/or leukemia- (eg, CHD2, CBX8, and EPC1) specific expression of several epigenetic factors. In addition, we show that several epigenetic factors use alternative transcription start sites in different cell types. This analysis could serve as a resource for the scientific community for further characterization of the role of these epigenetic factors in blood development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Lineage
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hematopoiesis / genetics*
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Principal Component Analysis
  • Transcription, Genetic