Torres, CM;
Biran, A;
Burney, MJ;
Patel, H;
Henser-Brownhill, T;
Cohen, A-HS;
Li, Y;
... Scaffidi, P; + view all
(2016)
The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity.
Science
, 353
(6307)
, Article aaf1644. 10.1126/science.aaf1644.
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Abstract
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.
Type: | Article |
---|---|
Title: | The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1126/science.aaf1644 |
Publisher version: | http://doi.org/10.1126/science.aaf1644 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Cancer Stem-cells, Tumor Heterogeneity, Differentiation, Glioblastoma, Evolution, Chromatin, Elements, RNA, DNA, Determinants |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1519949 |
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