Trabajo presentado en la VIII Jornada de Cromatina i Epigenètica, organizada por la Secció de Biologia Molecular de la Societat Catalana de Biologia (SCB) y celebrada el 16 de marzo de 2018Seven linker histone H1 variants exist in human somatic cells with distinct prevalence
depending on the cell type and along differentiation. H1 bind to linker DNA contributing to
higher order chromatin compaction. In addition, H1 seems to be actively involved in the
regulation of gene expression. It is not well known whether the different variants have
specific roles. We have shown that H1 variants are not distributed uniformly along the
genome and there are differences between variants, H1.2 being the one showing the most
specific pattern. We have explored functions of H1 variants by inducible shRNA-mediated
knock-down of each of the variants. Knock-down of each H1 variant alters expression of a
different, reduced subset of genes. Combined depletion of H1.2 and H1.4 has a strong
deleterious effect in the cancer cells examined, and induces a strong interferon (IFN)
response with up-regulation of many IFN-stimulated genes (ISGs). Although H1
participates to repress ISG promoters, its activation upon H1 KD is mainly generated by
the expression of noncoding RNA generated from heterochromatic repeats including
satellites. In conclusion, redundant H1-mediated silencing of heterochromatin is important
to maintain genome stability and to avoid an unspecific growth-inhibiting IFN response.N