期刊
GENES & DEVELOPMENT
卷 28, 期 7, 页码 723-734出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.236869.113
关键词
CTCF; RNA binding; Wrap53; p53; multimerization
资金
- National Institute of Health (NIH) [GM-64844, R37-37120]
- Howard Hughes Medical Institute
- Direccion General de Asuntos del Personal Academico-Universidad Nacional Autonoma de Mexico [IN209403, IN203811]
- Consejo Nacional de Ciencia y Tecnologia, Mexico (CONACyT) [42653-Q, 128464]
- CONACyT [213029]
- Direccion General de Estudios de Posgrado-Universidad Nacional Autonoma de Mexico (DGEP) [207989]
- Helen Hay Whitney Foundation
- Helen L. and Martin S. Kimmel Center for Stem Cell Biology
- NIH training grant from the Graduate Program in Cellular and Molecular Biology [T32 GM007238]
- PhD Graduate Program Doctorado en Ciencias Bioquimicas
The multifunctional CCCTC-binding factor (CTCF) protein exhibits a broad range of functions, including that of insulator and higher-order chromatin organizer. We found that CTCF comprises a previously unrecognized region that is necessary and sufficient to bind RNA (RNA-binding region [RBR]) and is distinct from its DNA-binding domain. Depletion of cellular CTCF led to a decrease in not only levels of p53 mRNA, as expected, but also those of Wrap53 RNA, an antisense transcript originated from the p53 locus. PAR-CLIP-seq (photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation [PAR-CLIP] combined with deep sequencing) analyses indicate that CTCF binds a multitude of transcripts genome-wide as well as to Wrap53 RNA. Apart from its established role at the p53 promoter, CTCF regulates p53 expression through its physical interaction with Wrap53 RNA. Cells harboring a CTCF mutant in its RBR exhibit a defective p53 response to DNA damage. Moreover, the RBR facilitates CTCF multimerization in an RNA-dependent manner, which may bear directly on its role in establishing higher-order chromatin structures in vivo.
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