title: Noncoding RNAs and LRRFIP1 regulate TNF expression.
abstract: Noncoding RNAs have been implicated in the regulation of expression of numerous genes; however, the mechanism is not fully understood. We identified bidirectional, long noncoding 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 noncoding RNAs were polyadenylated, capped, and chromatin associated. Knockdown of the noncoding RNAs was associated with derepression of TNF mRNA and diminished binding of LRRFIP1 to both RNA targets and chromatin. Overexpression of the noncoding RNAs led to diminished expression of TNF and recruitment of repressor proteins to the locus. One repressor protein, LRRFIP1, bound directly to the noncoding RNAs. These data place the noncoding 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.
authors.affiliation: Division of Allergy Immunology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Michael
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: Kelly
authors.initials: K
authors.lastname: Maurer
authors.forename: Asen
authors.initials: A
authors.lastname: Bagashev
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; C114370:LRRFIP1 protein, human; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha