Extended Data Figure 6: Epigenetic features of chromosomal integration sites of intact proviruses from ECs.

(a-d): Numbers of DNA sequencing reads associated with activating (H3K27ac) or repressive (H3K27me3) histone protein modifications in proximity to integration sites from ECs and long-term ART-treated individuals; median and confidence intervals (defined by one standard deviation) of ChIP-Seq data from primary memory CD4⁺ T-cells included in the ROADMAP repository²⁵ are shown. Negative distances indicate genomic regions upstream of the HIV 5’ LTR host-viral junction, while positive distances indicate regions downstream of the 3’ LTR viral-host junction. DNA sequencing reads associated with H3K36me3, an activating chromatin mark that is atypically enriched in KRAB-ZNF genes on Chromosome 19, are also shown²⁸. (e-f): Proportions of intact proviral sequences located in structural compartments A and B (and associated sub-compartments) by counting clonal sequences once (e) or by counting clonal sequences individually (f), as determined based on alignment of chromosomal integration sites of intact proviruses to Hi-C-Seq data from Jurkat cells²⁹. Chromosomal integration regions not covered in the Jurkat cell study were excluded from the analysis. Compartment B4 was not assessed in the source data²⁹ for this analysis. Two-sided Fisher’s exact tests were used for statistical comparisons, nominal p-values are reported. (a-f): Sequences in genomic regions included in the blacklist for functional genomics analysis identified by the ENCODE and modENCODE consortia²⁷ were excluded due to absence of reliable ChIP-Seq and Hi-C-Seq reads in such repetitive regions.