The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity

• DOI: 10.1126/science.aaf1644
• Publication Date: 2016-09-29T18:19:04Z
• Authors: Cristina Morales ...; Alva Biran; Matthew J. Burney; Harshil Patel; Tristan Henser-Br...; Ayelet-Hashahar S...; Yilong Li; Rotem Ben-Hamo; Emma Nye; Bradley Spencer-Dene; Probir Chakravarty; Sol Efroni; Nik Matthews; Tom Misteli; Eran Meshorer; Paola Scaffidi
• Keywords: Derepression; Epigenesis; Cancer Epigenetics

Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which within a tumor can sustain long-term cancer growth. Numerous types exhibit high inter- and intratumor heterogeneity H1.0, levels correlating differentiation status, patient survival, and, at single-cell level, stem cell markers. Silencing promotes maintenance self-renewing inducing derepression megabase-sized gene domains harboring downstream effectors oncogenic pathways. Self-renewing are not stable, reexpression in subsets establishes transcriptional programs restrict cells' potential drive their differentiation. Our results uncover determinants tumor-maintaining cells.