Identifying the role of telomere-chromatin interaction in the alteration of histone mark H3K4me3
Telomeres are TTAGGG repeat sequences positioned at the ends of human chromosomes to protect genomic integrity. They comprise constitutive heterochromatin, which recent studies indicate may alter transcription and thus silence genes where telomeres contact euchromatin. Telomere-chromatin interactions have been linked to altered expression in genes relatively distal to subtelomeres. The telomere position effect – over long distances (TPE-OLD) hypothesis proposes telomeres may therefore not be linear in conformation, but rather possess a curvature that results in the distal gene expression alterations. Our lab’s previous study profiled coverage of telomere-chromatin interaction on a whole-genome scale, identifying increased coverage near promoter regions of epigenetic features of interest, including the H3K4me3 histone mark commonly associated with transcriptional activation. This study analyzes H3K4me3 to investigate whether telomere-chromatin interactions are associated with transcriptional activation or suppression. H3K4me3 ChIP-seq data from an IMR-90 fibroblast cell line is processed utilizing an in-house pipeline, and aligned with the telomere-to-telomere (T2T) reference human genome. MACS2 calls over 40,000 significant peaks indicating H3K4me3 enrichment, spanning 3,168 promoter regions. Averaged peak coverage for both telomere-chromatin and H3K4me3 enrichment is visualized relative to transcriptional start sites. Increased telomere-chromatin interaction is observed to be associated with H3K4me3 enrichment in the active promoter region.
