CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

ELife
Gabriel N AugheyTony D Southall

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.

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Citations

Sep 7, 2018·Development·Seth W CheethamAndrea H Brand
Nov 30, 2019·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·David C Klein, Sarah J Hainer
Mar 17, 2019·Development·Gabriel N AugheyTony D Southall
Jan 25, 2020·Science·Gunsagar S GulatiAaron M Newman
Nov 13, 2020·Science Advances·Anoumid VaziriMonica Dus
Apr 30, 2020·Trends in Biochemical Sciences·Ruth NussinovHyunbum Jang
Dec 19, 2020·Current Opinion in Genetics & Development·Peter Askjaer, Jennifer C Harr
Sep 27, 2020·Current Opinion in Insect Science·Matthew J Niederhuber, Daniel J McKay
Nov 11, 2020·Developmental Cell·James P ReddingtonEileen E M Furlong

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Methods Mentioned

BETA
DamID
transgenic
FAIRE-seq
chemical fixation
immunoprecipitation
dissection
PCR

Software Mentioned

DamID
MEME
Excel
ggplot2
Morpheus
ATAC
CATaDa
R
SeqPlots R
deepTools

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