CCCTC-binding factor is an upstream regulator of the pluripotency factor Oct4 and functions in active transcription of linc1253 and linc1356 genes in pluripotent cells

Abstract

The embryonic stem cell- (ESC) specific transcription factor Oct4 is a well-known master regulator of pluripotency. The aim of this study was to identify upstream regulators of Oct4 and explore their functional link in regulating lincRNA expression in ESCs. By quantitative real-time PCR (RT-qPCR) analysis upon CCCTC-binding factor (CTCF) or Oct4 knockdown, here, we found that the chromatin insulator CTCF transcriptionally controls Oct4 gene expression in mouse ES cells. Furthermore, co-immunoprecipitation assays showed that CTCF physically interacts with Oct4. By analyzing CTCF and Oct4 ChIP-seq datasets in mouse ES cells and investigating their genomic occupancies, we demonstrated that CTCF and Oct4 share overlapping regulatory functions and are required for active transcription of long intergenic non-coding RNAs (lincRNAs) linc1253 and linc1356, which were reported to repress cellular lineage programs and maintain a pluripotent state. In summary, we propose an integrated model of transcriptional control mediated by CTCF, the master weaver of the genome, for the upstream regulation of Oct4-and ESC-associated genes. These results connect the chromatin insulator CTCF and the pluripotency factor Oct4 in the regulation of lincRNAs in pluripotent cells.