Multi-omics characterization of histone H1 variants genomic distribution and their contribution to chromatin compartmentalization and transposable elements regulation

The human histone H1 family comprises up to seven somatic subtypes. Using an integrative multi-omics approach that incorporates ChIP-Seq, Hi-C, RNA-Seq, and ATAC-Seq data, this thesis explores the genome-wide distribution and functional implications of six endogenous H1 variants in T47D breast cancer cells. Our results reveal that H1 variants can be divided into two groups based on the local GC content: H1.4 and H1X are enriched in high-GC regions, while H1.0, H1.2, H1.3, and H1.5 are abundant in low-GC regions. Notably, H1X is enriched within recently incorporated transposable elements and appears to play a role in their repression. We also evaluated the effects of depleting multiple H1 variants, observing more isolated but decompacted chromatin structures at the TAD level, which resulted in a coordinated transcriptional response within these domains. Our findings elucidate the complex relationship between histone H1 distribution, chromatin architecture, and transcription regulation, supporting that H1 variants have functional specificities depending on the genomic context rather than merely acting as simple chromatin compactors.