Transcription Of Angiogenin And Ribonuclease 4 Is Regulated By Rna Polymerase Iii Elements And A Ctcf-Dependent Intragenic Chromatin Loop

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA 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 the same promoters but their structure and regulation are unknown. We have characterized the promoters, 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 regulate 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 regulate 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. Citation Format: Jinghao Sheng, Chi Luo, Yuxiang Jiang, Philip W. Hinds, Zhengping Xu, Guo-fu Hu. Transcription of angiogenin and ribonuclease 4 is regulated by RNA polymerase III elements and a CTCF-dependent intragenic chromatin loop. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1401. doi:10.1158/1538-7445.AM2014-1401