The CSB chromatin remodeler and CTCF architectural protein cooperate in response to oxidative stress

TY - JOUR

T1 - The CSB chromatin remodeler and CTCF architectural protein cooperate in response to oxidative stress

AU - Lake, Robert J

AU - Boetefuer, Erica L

AU - Won, Kyoung-Jae

AU - Fan, Hua-Ying

N1 - © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2015/11/17

Y1 - 2015/11/17

N2 - Cockayne syndrome is a premature aging disease associated with numerous developmental and neurological abnormalities, and elevated levels of reactive oxygen species have been found in cells derived from Cockayne syndrome patients. The majority of Cockayne syndrome cases contain mutations in the ATP-dependent chromatin remodeler CSB; however, how CSB protects cells from oxidative stress remains largely unclear. Here, we demonstrate that oxidative stress alters the genomic occupancy of the CSB protein and increases CSB occupancy at promoters. Additionally, we found that the long-range chromatin-structure regulator CTCF plays a pivotal role in regulating sites of genomic CSB occupancy upon oxidative stress. We show that CSB directly interacts with CTCF in vitro and that oxidative stress enhances the CSB-CTCF interaction in cells. Reciprocally, we demonstrate that CSB facilitates CTCF-DNA interactions in vitro and regulates CTCF-chromatin interactions in oxidatively stressed cells. Together, our results indicate that CSB and CTCF can regulate each other's chromatin association, thereby modulating chromatin structure and coordinating gene expression in response to oxidative stress.

AB - Cockayne syndrome is a premature aging disease associated with numerous developmental and neurological abnormalities, and elevated levels of reactive oxygen species have been found in cells derived from Cockayne syndrome patients. The majority of Cockayne syndrome cases contain mutations in the ATP-dependent chromatin remodeler CSB; however, how CSB protects cells from oxidative stress remains largely unclear. Here, we demonstrate that oxidative stress alters the genomic occupancy of the CSB protein and increases CSB occupancy at promoters. Additionally, we found that the long-range chromatin-structure regulator CTCF plays a pivotal role in regulating sites of genomic CSB occupancy upon oxidative stress. We show that CSB directly interacts with CTCF in vitro and that oxidative stress enhances the CSB-CTCF interaction in cells. Reciprocally, we demonstrate that CSB facilitates CTCF-DNA interactions in vitro and regulates CTCF-chromatin interactions in oxidatively stressed cells. Together, our results indicate that CSB and CTCF can regulate each other's chromatin association, thereby modulating chromatin structure and coordinating gene expression in response to oxidative stress.

KW - Base Sequence

KW - Binding Sites

KW - CCCTC-Binding Factor

KW - Cell Line, Transformed

KW - Chromatin/chemistry

KW - Chromatin Assembly and Disassembly/drug effects

KW - DNA/genetics

KW - DNA Helicases/genetics

KW - DNA Repair Enzymes/genetics

KW - Fibroblasts/cytology

KW - Gene Expression Regulation

KW - Humans

KW - Molecular Sequence Data

KW - Oxidative Stress

KW - Poly-ADP-Ribose Binding Proteins

KW - Protein Binding

KW - RNA, Small Interfering/genetics

KW - Repressor Proteins/antagonists & inhibitors

KW - Signal Transduction

KW - Vitamin K 3/pharmacology

U2 - 10.1093/nar/gkv1219

DO - 10.1093/nar/gkv1219

M3 - Journal article

C2 - 26578602

SN - 0305-1048

VL - 44

SP - 2125

EP - 2135

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 5

ER -