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The role of chromatin dynamics in immune cell development
Author(s) -
Winter Deborah R.,
Amit Ido
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12200
Subject(s) - chromatin , biology , epigenomics , enhancer , histone , histone modifying enzymes , bivalent chromatin , nucleosome , microbiology and biotechnology , chia pet , epigenetics , cellular differentiation , histone code , genetics , computational biology , gene , dna methylation , transcription factor , gene expression
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 DN ase‐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.