CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response.

Nature Genetics
Grégoire StikThomas Graf

Abstract

Three-dimensional organization of the genome is important for transcriptional regulation1-7. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs)8-12. Although TADs can contribute to transcriptional regulation, ablation of TAD organization by disrupting CTCF or the cohesin complex causes modest gene expression changes13-16. In contrast, CTCF is required for cell cycle regulation17, embryonic development and formation of various adult cell types18. To uncouple the role of CTCF in cell-state transitions and cell proliferation, we studied the effect of CTCF depletion during the conversion of human leukemic B cells into macrophages with minimal cell division. CTCF depletion disrupts TAD organization but not cell transdifferentiation. In contrast, CTCF depletion in induced macrophages impairs the full-blown upregulation of inflammatory genes after exposure to endotoxin. Our results demonstrate that CTCF-dependent genome topology is not strictly required for a functional cell-fate conversion but facilitates a rapid and efficient response to an external stimulus.

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Citations

Jan 27, 2021·Current Opinion in Genetics & Development·Gabriel R CavalheiroEileen Em Furlong
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Yuki Fujita, Toshihide Yamashita
Jan 6, 2021·Nature Structural & Molecular Biology·Naoki KuboBing Ren
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Nov 20, 2020·Cell Systems·Christopher P JohnstoneKate E Galloway
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May 14, 2021·Developmental Cell·Erin Aboelnour, Boyan Bonev
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Methods Mentioned

BETA
Hi-C
PCA
RNA-seq
flow cytometry
GTPase
transfection
PCR
genotyping
fluorescence-activated cell sorting
electrophoresis

Software Mentioned

deepTools
HiChIP
sva R package
Trimmomatic
HiCExplorer
SciPy
Diffbind R package
hicAggregateContacts
OneD
Bowtie2

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