TY - JOUR T1 - Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion JF - bioRxiv DO - 10.1101/2021.02.12.429879 SP - 2021.02.12.429879 AU - Núria Serna-Pujol AU - Mónica Salinas-Pena AU - Francesca Mugianesi AU - François Le Dily AU - Marc A. Marti-Renom AU - Albert Jordan Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/24/2021.02.12.429879.abstract N2 - Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local DNA GC content and that their distribution is robust with respect to multiple H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of Topologically Associating Domains or TADs. Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants within a cell line and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.Competing Interest StatementThe authors have declared no competing interest. ER -