The role of chromatin dynamics in immune cell development

Deborah R. Winter, Ido Amit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Summary: In immune cells, as in all mammalian cells, nuclear DNA is wrapped around histones to form nucleosomes. The positioning and modifications of nucleosomes throughout the genome defines the chromatin state of the cell and has a large impact on gene regulation. Chromatin state is dynamic throughout immune cell development and activation. High-throughput open chromatin assays, such as DNase-seq, can be used to find regulatory element across the genome and, when combined with histone modifications, can specify their function. During hematopoiesis, distal regulatory elements, known as enhancers, are established by pioneer factors that alter chromatin state. Some of these enhancers are lost, some are gained, and some are maintained as a memory of the cell's developmental origin. The enhancer landscape is unique to the cell lineage-with different enhancers regulating the same promoter-and determines the mechanism of cell type-specific activation after exposure to stimuli. Histone modification and promoter architecture govern the diverse responses to stimulation. Furthermore, chromatin dynamics may explain the high plasticity of certain tissue-resident immune cell types. Future epigenomic research will depend on the development of more efficient experiments and better methods to associate enhancers with genes. The ultimate goal of mapping genome-wide chromatin state throughout the hematopoietic tree will help illuminate the mechanisms behind immune cell development and function.

Original languageEnglish (US)
Pages (from-to)9-22
Number of pages14
JournalImmunological Reviews
Volume261
Issue number1
DOIs
StatePublished - Sep 2014

Keywords

  • Chromatin
  • Hematopoietic tree
  • Histone modifications
  • Pioneer factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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