CATaDa Reveals Global Remodelling of Chromatin Accessibility During Stem Cell Differentiation in Vivo

Elife. 2018 Feb 26;7:e32341. doi: 10.7554/eLife.32341.

Abstract

During development eukaryotic gene expression is coordinated by dynamic changes in chromatin structure. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic lineages are not well defined. Here we show that cell-specific chromatin accessibility data can be produced via ectopic expression of E. coli Dam methylase in vivo, without the requirement for cell-sorting (CATaDa). We have profiled chromatin accessibility in individual cell-types of Drosophila neural and midgut lineages. Functional cell-type-specific enhancers were identified, as well as novel motifs enriched at different stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their differentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell differentiation and provide a novel approach to understanding gene regulatory mechanisms underlying development.

Keywords: D. melanogaster; chromatin accessibility; chromosomes; developmental biology; differentiation; genes; neural development; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Chromatin / metabolism*
  • Drosophila / embryology*
  • Epigenesis, Genetic*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Pluripotent Stem Cells / physiology*
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / metabolism
  • Staining and Labeling

Substances

  • Chromatin
  • Escherichia coli Proteins
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
  • dam protein, E coli