title: Transcription of angiogenin and ribonuclease 4 is regulated by RNA polymerase III elements and a CCCTC binding factor (CTCF)-dependent intragenic chromatin loop.
abstract: Angiogenin (ANG) and ribonuclease 4 (RNASE4), two members of the secreted and vertebrate-specific ribonuclease superfamily, play important roles in cancers and neurodegenerative diseases. The ANG and RNASE4 genes share genetic regions with promoter activities, but the structure and regulation of these putative promotes are unknown. We have characterized the promoter regions, defined the transcription start site, and identified a mechanism of transcription regulation that involves both RNA polymerase III (Pol III) elements and CCCTC binding factor (CTCF) sites. We found that two Pol III elements within the promoter region influence ANG and RNASE4 expression in a position- and orientation-dependent manner. We also provide evidence for the presence of an intragenic chromatin loop between the two CTCF binding sites located in two introns flanking the ANG coding exon. We found that formation of this intragenic loop preferentially enhances ANG transcription. These results suggest a multilayer transcriptional regulation of ANG and RNASE4 gene locus. These data also add more direct evidence to the notion that Pol III elements are able to directly influence Pol II gene transcription. Furthermore, our data indicate that a CTCF-dependent chromatin loop is able to differentially regulate transcription of genes that share the same promoters.
authors.affiliation: From the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111 and.
authors.forename: Jinghao
authors.initials: J
authors.lastname: Sheng
authors.forename: Chi
authors.initials: C
authors.lastname: Luo
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Philip W
authors.initials: PW
authors.lastname: Hinds
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
authors.forename: Guo-fu
authors.initials: GF
authors.lastname: Hu
mesh_terms: D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012320:RNA Polymerase III / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D012260:Ribonucleases / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D012097:Repressor Proteins; D014157:Transcription Factors; D008156:Luciferases; D012319:RNA Polymerase II; D012320:RNA Polymerase III; D012260:Ribonucleases; C083939:ribonuclease 4; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Angiogenin; Chromatin; Promoters; RNA Polymerase; Ribonuclease; Rinonuclease 4; Transcription