Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

Epigenetics Chromatin. 2020 Jan 9;13(1):1. doi: 10.1186/s13072-019-0325-2.


Background: Chromatin organization is central to precise control of gene expression. In various eukaryotic species, domains of pervasive cis-chromatin interactions demarcate functional domains of the genomes. In nematode Caenorhabditis elegans, however, pervasive chromatin contact domains are limited to the dosage-compensated sex chromosome, leaving the principle of C. elegans chromatin organization unclear. Transcription factor III C (TFIIIC) is a basal transcription factor complex for RNA polymerase III, and is implicated in chromatin organization. TFIIIC binding without RNA polymerase III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remains unknown.

Results: We identified 504 TFIIIC-bound sites absent of RNA polymerase III and TATA-binding protein co-occupancy characteristic of extra-TFIIIC sites in C. elegans embryos. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Extra-TFIIIC sites formed dense clusters in cis. The clusters of extra-TFIIIC sites were highly over-represented within the distal arm domains of the autosomes that presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions.

Conclusion: Clusters of extra-TFIIIC sites were pervasive in the arm domains of C. elegans autosomes, near the outer boundaries of H3K9me3-marked regions. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans.

Keywords: Caenorhabditis elegans; Chromatin; Chromosome; Histone H3 lysine 9 methylation; Insulator; LEM-2; Lamina-associated domain; Nuclear periphery; RNA polymerase III; Transcription factor III C (TFIIIC).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism*
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism*
  • Histones / chemistry
  • Histones / metabolism
  • Nuclear Lamina / metabolism
  • Protein Binding
  • Transcription Factors, TFIII / metabolism*


  • Caenorhabditis elegans Proteins
  • Heterochromatin
  • Histones
  • Transcription Factors, TFIII
  • transcription factor TFIIIC