Abstract
Transcription factors (TFs) bind DNA in a sequence-specific manner and are generally cell type-specific factors and/or developmental master regulators. In contrast, general TFs (GTFs) are part of very large protein complexes and serve for RNA polymerases’ recruitment to promoter sequences, generally in a cell type-independent manner. Whereas, several TFs have been proven to serve as anchors for the 3D genome organization, the role of GTFs in genome architecture have not been carefully explored. Here, we used ChIP-seq and Hi-C data to depict the role of TFIIIC, one of the RNA polymerase III GTFs, in 3D genome organization. We find that TFIIIC genome occupancy mainly occurs at specific regions, which largely correspond to Alu elements; other characteristic classes of repetitive elements (REs) such as MIR, FLAM-C and ALR/alpha are also found depending on the cell’s developmental origin. The analysis also shows that TFIIIC-enriched regions are involved in cell type-specific DNA looping, which does not depend on colocalization with the master architectural protein CTCF. This work extends previous knowledge on the role of TFIIIC as a bona fide genome organizer whose action participates in cell type-dependent 3D genome looping via binding to REs.
Highlights
Three-dimensional folding of the mammalian genome acts as a decisive regulatory layer for determining important physiological processes such as cell fate, development, differentiation, and even pathological conditions such as tumorigenesis, by implementing cell-type specific gene expression programs [1]
Our analysis shows that TFIIIC acts as a cell type-specific factors (CTFs) by binding to cell typeexpressed repetitive elements (REs), which largely correspond to Alu elements (AE), and to distinctive REs classes such as
The presence of the TFIIIC complex on chromatin was detected with a rabbit polyclonal antibody raised against the N-terminal 477 amino acids of the second largest subunit of TFIIIC (TFIIIC110 or GTF3C2) [19]
Summary
Three-dimensional folding of the mammalian genome acts as a decisive regulatory layer for determining important physiological processes such as cell fate, development, differentiation, and even pathological conditions such as tumorigenesis, by implementing cell-type specific gene expression programs [1]. The first two classes of TFs can be expressed ubiquitously or be cell type-specific factors (CTFs), whereas GTFs are expressed in every single cell of the organism [2–4]. The actions of CTFs are largely studied and depend on the overwhelming number of distinct and specific DNA binding sites on regulatory regions, either in the promoter regions or tens to hundreds of kilobases away from the promoters they activate [5–7]. The latter are known as enhancers and/or super-enhancers and they are referred to as regulatory distal enhancers elements (DEEs)
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