Document Type
Article
Publication Date
2-19-2020
Keywords
JGM, JAXCC
JAX Source
Sci Adv 2020 Feb 19; 6(8):eaaw4651
Volume
6
Issue
8
First Page
4651
Last Page
4651
ISSN
2375-2548
PMID
32128389
DOI
https://doi.org/10.1126/sciadv.aaw4651
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.
Recommended Citation
Luo H,
Yu Q,
Liu Y,
Tang M,
Liang M,
Zhang D,
Xiao T,
Wu L,
Tan M,
Ruan Y,
Bungert J,
Lu J.
LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding. Sci Adv 2020 Feb 19; 6(8):eaaw4651
Comments
This open access article is licensed under a Creative Commons Attribution 4.0 International License