Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells

Genome wide analysis of human RNA Polymerase III (Pol) reveals both known and new targets of Pol III, with many of the latter binding regions found near SINEs. Active Pol III genes are near active Pol II promoters, whereas inactive Pol III genes are not. ETC loci, which are bound by TFIIIC but not TFIIIB and Pol III, are near active Pol II promoters and CTCF binding sites. Genome-wide occupancy profiles of five components of the RNA polymerase III (Pol III) machinery in human cells identified the expected tRNA and noncoding RNA targets and revealed many additional Pol III–associated loci, mostly near short interspersed elements (SINEs). Several genes are targets of an alternative transcription factor IIIB (TFIIIB) containing Brf2 instead of Brf1 and have extremely low levels of TFIIIC. Strikingly, expressed Pol III genes, unlike nonexpressed Pol III genes, are situated in regions with a pattern of histone modifications associated with functional Pol II promoters. TFIIIC alone associates with numerous ETC loci, via the B box or a novel motif. ETC s are often near CTCF binding sites, suggesting a potential role in chromosome organization. Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner.