An RNA Polymerase III General Transcription Factor Engages in Cell Type-Specific Chromatin Looping

Transcription factors (TFs) bind DNA in a sequence-specific manner and have been proven to serve as anchors to the 3D genome organization. These TFs are generally cell type-specific factor and/or developmental master regulators. General TFs (GTFs) which serve RNA polymerase recruitment to specific promoter sequences, however, can be part of very large protein complexes but their roles in genome architecture have not been carefully explored. Here, we used a bio-informatic approach of ChIP-seq and Hi-C data analysis to depict the role of one GTF of the RNA polymerase III system (TFIIIC) in several human cell lines, both normal and transformed. We find that TFIIIC occupancy within the genome mainly occurs at specific regions which largely correspond to Alu elements but also at characteristic classes of repetitive elements (REs) such as MIR, FLAMC and ALR/alpha, depending on the cell’s developmental origin. We then show that these TFIIIC-enriched regions are involved in cell type-specific DNA looping within the genome and do not depend on colocalization with the master architectural protein CTCF. This work extends previous knowledge about the role of TFIIIC as a bona fide genome organizer whose action can lead to cell type-dependent 3D genome looping via binding to REs. Examination of the role of TFIIIC in 3D genome organization