The linker histone H1.0 generates epigenetic and functional intratumor heterogeneityMore about Open Access at the Crick
Authors listCristina Morales Torres Alva Biran Matthew J Burney Harshil Patel Tristan Henser-Brownhill Ayelet-Hashahar Shapira Cohen Yilong Li Rotem Ben-Hamo Emma Nye Bradley Spencer-Dene Probir Chakravarty Sol Efroni Nik Matthews Tom Misteli Eran Meshorer Paola Scaffidi
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 cells within a tumor can sustain the long-term cancer growth. Numerous cancer types exhibit high inter- and intratumor heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation status, patient survival, and, at the single-cell level, cancer stem cell markers. Silencing of H1.0 promotes maintenance of self-renewing cells by inducing derepression of megabase-sized gene domains harboring downstream effectors of oncogenic pathways. Self-renewing epigenetic states are not stable, and reexpression of H1.0 in subsets of tumor cells establishes transcriptional programs that restrict cancer cells' long-term proliferative potential and drive their differentiation. Our results uncover epigenetic determinants of tumor-maintaining cells.
Issue number 6307