CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53.
CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53.
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DOI:
10.1101/gad.236869.113
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发表时间:
2014-04-01
影响因子:
10.5
通讯作者:
Reinberg D
中科院分区:
文献类型:
--
作者:
Saldaña-Meyer R;González-Buendía E;Guerrero G;Narendra V;Bonasio R;Recillas-Targa F;Reinberg D
The CTCF protein functions as an insulator and higher-order chromatin organizer. Reinberg and colleagues report that in addition to its DNA-binding activity, CTCF binds RNA. They map the RNA-binding domain and demonstrate that apart from its established role at the p53 promoter, CTCF regulates p53 expression through its physical interaction with the Wrap53 RNA. Furthermore, the authors show that the RNA-binding domain facilitates CTCF multimerization in an RNA-dependent manner, which may bear directly on its role in establishing higher-order chromatin structures. 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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通讯作者:
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