Noncoding RNAs and LRRFIP1 regulate TNF expression.
Noncoding RNAs and LRRFIP1 regulate TNF expression.
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DOI:
10.4049/jimmunol.1302063
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发表时间:
2014-04-01
期刊:
影响因子:
--
通讯作者:
Sullivan KE
中科院分区:
文献类型:
--
作者:
Shi L;Song L;Fitzgerald M;Maurer K;Bagashev A;Sullivan KE
Non-coding RNAs have been implicated in the regulation of expression of numerous genes, however, the mechanism is not fully understood. We identified bidirectional, long non-coding RNAs upstream of the TNF gene using five different methods. They arose in a region where the repressors LRRFIP1, EZH2, and SUZ12 were demonstrated to bind, suggesting a role in repression. The non-coding RNAs were polyadenylated, capped, and chromatin-associated. Knock-down of the non-coding RNAs was associated with de-repression of TNF mRNA and diminished binding of LRRFIP1 to both RNA targets and chromatin. Over-expression of the non-coding RNAs led to diminished expression of TNF and recruitment of repressor proteins to the locus. One repressor protein, LRRFIP1, bound directly to the non-coding RNAs. These data place the non-coding RNAs upstream of TNF gene as central to the transcriptional regulation. They appear to serve as a platform for the assembly of a repressive complex.
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