TFIIIC regulates SMC complex binding and 3D DNA contacts between tRNA genes

Transcription factor IIIC (TFIIIC) is a multi-subunit protein complex that recruits RNA polymerase III (Pol III) to the majority of its target genes. Evolutionarily conserved overlap between TFIIIC binding sites and the structural maintenance of chromosomes (SMC) complexes suggested a role for TFIIIC in SMC regulation and 3D organization of eukaryotic genomes; but the evidence has remained largely correlational due to the essential role of TFIIIC in RNA Pol III transcription. Here, we directly tested the function of TFIIIC in SMC complex regulation by using auxin inducible depletion in C. elegans. We performed Hi-C and ChIP-seq analyses upon acute depletion of TFTC-3, an essential TFIIIC subunit, and RPC-1, the catalytic subunit of RNA Pol III. Our results show that TFIIIC regulates the localization of two different types of SMC complexes, cohesin and condensin. TFIIIC is also required for increased 3D contacts between distant tRNA genes located on the same or different chromosomes. Depletion of individual SMC complexes did not significantly reduce the intrachromosomal tRNA gene contacts, suggesting redundancy or an independent mechanism mediating these contacts. Together, our study demonstrates an RNA Pol III independent function for TFIIIC, regulating binding of both cohesin and condensin, as well as the 3D organization of tRNA genes.