LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding

Science Advances
Huacheng LuoJianrong Lu

Abstract

Chromatin topological organization is instrumental in gene transcription. Gene-enhancer interactions are accommodated in the same CTCF-mediated insulated neighborhoods. However, it remains poorly understood whether and how the 3D genome architecture is dynamically restructured by external signals. Here, we report that LATS kinases phosphorylated CTCF in the zinc finger (ZF) linkers and disabled its DNA-binding activity. Cellular stress induced LATS nuclear translocation and CTCF ZF linker phosphorylation, and altered the landscape of CTCF genomic binding partly by dissociating it selectively from a small subset of its genomic binding sites. These sites were highly enriched for the boundaries of chromatin domains containing LATS signaling target genes. The stress-induced CTCF phosphorylation and locus-specific dissociation from DNA were LATS-dependent. Loss of CTCF binding disrupted local chromatin domains and down-regulated genes located within them. The study suggests that external signals may rapidly modulate the 3D genome by affecting CTCF genomic binding through ZF linker phosphorylation.

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Citations

Jan 8, 2021·Frontiers in Cell and Developmental Biology·Tanaya Roychowdhury, Samit Chattopadhyay
Dec 2, 2020·Current Opinion in Genetics & Development·Jian-Feng Xiang, Victor G Corces
Jun 1, 2021·Frontiers in Molecular Biosciences·Niko LinzerJörg Bungert
Aug 11, 2021·Biochemical Society Transactions·Jiwon Park, Carsten Gram Hansen

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Datasets Mentioned

BETA
GSE112295
GSE114319
TEAD4

Methods Mentioned

BETA
immunoprecipitation
nuclear translocation
ChIP
acetylation
PCR
reverse transcription PCR
electrophoresis
ChIP-seq

Software Mentioned

DEseq2
BEDTools
bigWig
Database for Annotation , Visualization and Integrated Discove...
HOMER
package
FastQC
BamCoverage
Intergrative Genomics Viewer
Excel

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