Featured
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Article |
Histone demethylase KDM5D upregulation drives sex differences in colon cancer
A murine colorectal cancer (CRC) model shows that mutant KRAS-STAT4-mediated upregulation of Y chromosome KDM5D contributes to the sex differences in KRAS-mutant CRC, providing an actionable therapeutic strategy for metastasis risk reduction for men afflicted with KRAS-mutant CRC.
- Jiexi Li
- , Zhengdao Lan
- & Ronald A. DePinho
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Article |
BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network
BRD8 is identified as a specific epigenetic vulnerability for glioblastomas that harbour wild-type p53.
- Xueqin Sun
- , Olaf Klingbeil
- & Alea A. Mills
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Article |
ecDNA hubs drive cooperative intermolecular oncogene expression
Extrachromosomal DNA (ecDNA) congregates in clusters called ecDNA hubs that promote intermolecular interactions between gene-regulatory regions and thereby amplify the expression of oncogenes such as MYC in cancer cell lines.
- King L. Hung
- , Kathryn E. Yost
- & Howard Y. Chang
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Article |
A clinically applicable integrative molecular classification of meningiomas
Multi-omics datasets are integrated to generate a unified and clinically informed molecular classification of meningiomas.
- Farshad Nassiri
- , Jeff Liu
- & Gelareh Zadeh
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Article |
Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma
Analyses of samples from 728 women with uterine leiomyomas (uterine fibroids), and public data, show that somatic and germline mutations in the SRCAP histone-loading complex genes are associated with the condition.
- Davide G. Berta
- , Heli Kuisma
- & Lauri A. Aaltonen
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Article |
Phase separation drives aberrant chromatin looping and cancer development
The NUP98–HOXA9 oncogenic fusion protein found in leukaemia undergoes phase separation in the nucleus, which helps to promote activation of leukaemic genes and to establish aberrant chromatin looping.
- Jeong Hyun Ahn
- , Eric S. Davis
- & Gang Greg Wang
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Article |
Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity
A CRISPR–Cas9 screen of chromatin regulators in mouse tumour models treated with immune checkpoint blockade identifies SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity.
- Gabriel K. Griffin
- , Jingyi Wu
- & Bradley E. Bernstein
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Article |
Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture
Mutations in histone H1 induce the remodelling of chromatin architecture to a more relaxed state, which leads to malignant transformation through changes in histone modifications and the expression of stem cell genes.
- Nevin Yusufova
- , Andreas Kloetgen
- & Ari M. Melnick
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Article |
Oncometabolites suppress DNA repair by disrupting local chromatin signalling
Metabolites that are elevated in tumours inhibit the lysine demethylase KDM4B, resulting in aberrant hypermethylation of histone 3 lysine 9 and decreased homology-dependent DNA repair.
- Parker L. Sulkowski
- , Sebastian Oeck
- & Peter M. Glazer
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Article |
Impaired cell fate through gain-of-function mutations in a chromatin reader
The histone-acetylation-reader protein ENL is mutated in a paediatric kidney cancer in such a way that it clusters at target genes, increasing the recruitment of the transcriptional machinery, enhancing transcription and deregulating cell fate during development.
- Liling Wan
- , Shasha Chong
- & C. David Allis
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Letter |
Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis
Analyses of transcriptomes from patients with acute myeloid leukaemia identified frequently co-occurring mutations of IDH2 and SRSF2, which functional analyses showed to have distinct and coordinated leukaemogenic effects on the epigenome and RNA splicing.
- Akihide Yoshimi
- , Kuan-Ting Lin
- & Omar Abdel-Wahab
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Letter |
BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells
The CTCF paralogue BORIS is upregulated in transcriptionally reprogrammed neuroblastoma cells rendered resistant to targeted therapy, in which it promotes regulatory chromatin interactions that maintain the resistance phenotype.
- David N. Debruyne
- , Ruben Dries
- & Rani E. George
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Analysis |
The expanding landscape of ‘oncohistone’ mutations in human cancers
The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.
- Benjamin A. Nacev
- , Lijuan Feng
- & C. David Allis
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Article |
Necroptosis microenvironment directs lineage commitment in liver cancer
The tumour microenvironment determines which type of liver cancer develops, with transformed hepatocytes giving rise to intrahepatic cholangiocarcinoma or hepatocellular carcinoma depending or whether they are surrounded by cells undergoing necroptosis or apoptosis.
- Marco Seehawer
- , Florian Heinzmann
- & Lars Zender
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Letter |
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer
Modulation of DNA 5-hydroxymethylcytosine by glucose reveals an AMPK–TET2–5hmC axis that links diabetes to cancer.
- Di Wu
- , Di Hu
- & Yujiang Geno Shi
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Letter |
Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling
Super enhancers regulate oncogenes and other molecular targets in ependymomas, and identification of these genes provides potential therapeutic targets.
- Stephen C. Mack
- , Kristian W. Pajtler
- & Jeremy N. Rich
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Letter |
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer
Analysis of global remethylation in mouse embryos at several developmental stages identifies an epigenetic landscape that partitions extraembryonic tissues within the embryo and resembles a frequent, global departure in genome regulation in human cancers.
- Zachary D. Smith
- , Jiantao Shi
- & Alexander Meissner
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Letter |
Orthotopic patient-derived xenografts of paediatric solid tumours
A protocol producing orthotopic patient-derived xenografts at diagnosis, recurrence, and autopsy demonstrates proof of principle for using these tumours for basic and translational research on paediatric solid tumours.
- Elizabeth Stewart
- , Sara M. Federico
- & Michael A. Dyer
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Letter |
Transcription elongation factors represent in vivo cancer dependencies in glioblastoma
An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.
- Tyler E. Miller
- , Brian B. Liau
- & Jeremy N. Rich
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Letter |
Transcription control by the ENL YEATS domain in acute leukaemia
ENL, identified in a genome-scale loss-of-function screen as a crucial requirement for proliferation of acute leukaemia, is required for leukaemic gene expression, and its YEATS chromatin-reader domain is essential for leukaemic growth.
- Michael A. Erb
- , Thomas G. Scott
- & James E. Bradner
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Letter |
Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer
Depletion of Smarcb1 activates the Myc network of signalling cascades, increasing protein metabolism and activation of survival pathways allowing highly aggressive Kras-independent pancreatic cancer cells to develop.
- Giannicola Genovese
- , Alessandro Carugo
- & Lynda Chin
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Letter |
Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples
A DNase sequencing method termed scDNase-seq detects DNase I hypersensitive sites genome-wide in single cells and pools of cells dissected from cancer biopsies.
- Wenfei Jin
- , Qingsong Tang
- & Keji Zhao
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News Feature |
Cancer research: Open ambition
Jay Bradner believes that cancer can be defeated through control of epigenetics — and he is not shy about spreading the word.
- Amy Maxmen
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Feature |
Epigenetics: Marked for success
The growing field of cancer epigenetics demands computational expertise and translational research experience. Qualified practitioners are in high demand.
- Heidi Ledford
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Article
| Open Access
A novel retinoblastoma therapy from genomic and epigenetic analyses
The retinoblastoma genome is shown to be stable, but multiple cancer pathways are identified that are epigenetically deregulated, providing potential new therapeutic targets.
- Jinghui Zhang
- , Claudia A. Benavente
- & Michael A. Dyer
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Letter |
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
- Johannes Zuber
- , Junwei Shi
- & Christopher R. Vakoc
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Editorial |
Time for the epigenome
The complexity of genetic regulation is one of the great wonders of nature, but it represents a daunting challenge to unravel. The International Human Epigenome Consortium is an appropriate response.
Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF