Abstract
BackgroundChromatin 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.ResultsWe 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.ConclusionClusters 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.
Highlights
Chromatin organization is central to precise control of gene expression
Half of C. elegans Transcription factor III C (TFIIIC) binding sites lack Pol III co‐occupancy The TFIIIC complex is a general transcription factor required for the assembly of the RNA polymerase III (Pol III) machinery at small non-coding RNA genes such as tRNA genes (Fig. 1a)
We identified 1029 high-confidence TFIIIC-bound sites exhibiting strong and consistent enrichment for both TFTC-3 and TFTC-5 (Fig. 1c). tRNA genes were strongly enriched for TFTC-3, TFTC-5, Pol III, and TATA-binding protein (TBP) as expected (Fig. 1d)
Summary
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. The autosome arms are rich in repetitive elements [23] and heterochromatinassociated histone modifications [16, 27], and are associated with the nuclear membrane [18, 28, 29] Within these generally euchromatic centers and heterochromatic arms lie kilobase-wide regions of various chromatin states including transcriptionally active and inactive regions [3, 4]. A highly conserved class of architectural proteins [30], define the boundaries of TAD-like self-interacting domains in the X chromosome [22], the contribution of condensins to autosomal chromatin organization is unclear [14, 31]. How chromatin domains and chromatin states in the C. elegans autosomes are demarcated remains an area of active investigation [4, 28, 33, 34]
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