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. 2021 Jul 30;8:696438. doi: 10.3389/fmolb.2021.696438

FIGURE 2.

FIGURE 2

Promoters directing human RNA polymerase III transcription. Pol III type 1 and type 2 genes contain gene-internal promoter elements. (A) Type 1 gene transcription of 5S ribosomal (r)RNA is directed by A- and C-boxes that are located relative to the transcription start site (TSS) as indicated. These promoter elements are bound by TFIIIA, permitting the recruitment of TFIIIC and subsequently of TFIIIB-β (composed of TBP, BDP1 and BRF1), which altogether recruit Pol III. (B) Type 2 genes (tRNA genes, VA1, VA2, SINEs) contain A- and B-boxes as promoter elements at varying positions relative to the TSS. They are bound by TFIIIC, subsequently allowing recruitment of TFIIIB-β and in turn of Pol III. (C) Type 3 gene regulatory elements are entirely located upstream (5′) of the TSS. They are composed of a TATA-box at -30, as well as a proximal sequence element (PSE) and a distal sequence element (DSE) at variable distances with respect to the TSS, depending on the gene. Transcriptional activators (STAF/ZNF143; SNAPc/PTF) bind to the DSE and PSE, respectively, and regulate transcriptional activity. The TATA-box is the only promoter element required for directing Pol III to the TSS (Teichmann et al., 1997). It is bound by TFIIIB-α (composed of TBP, BDP1 and BRF2), which in turn recruits Pol III. (D) Hybrid promoter-directed transcription is regulated by gene-internal elements of type 2 promoters (A- and B-boxes) and additionally by gene regulatory elements upstream of the TSS. All these elements vary in their distance to the TSS depending on the gene. In the presence of the PSE (tRNASec gene), TFIIIB-α is recruited (not shown in the Figure). In the case of all other enhancer-activator combinations with gene-internal A- and B-boxes (EBER 1 and 2; 7SL; vault; BC1 and BC200), TFIIIB-β is recruited, allowing the subsequent recruitment of RNA polymerase III. For all promoter types, the stretch of T’s represents the transcription termination site. Arrows in panels C. and D. symbolize protein-protein-interactions that contribute to activation of Pol III transcription from these promoters. Promoter types were reviewed in Dumay-Odelot et al. (2014).