期刊
NATURE
卷 454, 期 7200, 页码 126-U11出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature06992
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [P30 CA008748, R01 CA052599-19, CA52599, CA097134, P30 CA08748, R01 CA052599] Funding Source: Medline
- NHLBI NIH HHS [HL59694, R01 HL059694-10, R01 HL059694] Funding Source: Medline
- NIDDK NIH HHS [DK39949, R37 DK039949, R37 DK039949-26, DK074868, R01 DK091183, R01 DK039949] Funding Source: Medline
- NINDS NIH HHS [R01 NS034934, R01 NS034934-20A1, NS34934] Funding Source: Medline
With the recent recognition of non- coding RNAs ( ncRNAs) flanking many genes(1-5), a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms(6-12). Here we show that an RNA- binding protein, TLS ( for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB- binding protein ( CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 ( CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene- specific repression is directed by single- stranded, low- copy- number ncRNA transcripts tethered to the 5' regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA- binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.
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