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The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin
The chromatin remodeling complex ATRX can promote gene expression, for example by binding G-quadruplexes (G4s) to prevent their negative effect on expression. Here the authors use a single-cell approach to show that only a subset of erythroid cells isolated from patients with ATRX mutations have reduced chromatin accessibility and alpha globin expression, suggesting a stochastic process.
- Julia Truch
- , Damien J. Downes
- & Richard J. Gibbons
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Article
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Common schizophrenia risk variants are enriched in open chromatin regions of human glutamatergic neurons
Here, the authors perform ATAC-seq on four distinct cell populations from three different regions of the human brain, finding that chromatin accessibility varies greatly by cell type and less by brain region. This study reveals differences in biological function and gene regulation, as well as overlap of genetic variants associated with schizophrenia and other neuropsychiatric traits.
- Mads E. Hauberg
- , Jordi Creus-Muncunill
- & Panos Roussos
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Article
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CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language
Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.
- Lot Snijders Blok
- , Justine Rousseau
- & Philippe M. Campeau
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Article
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DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer
Altered epigenetics is a feature of cancer but whether these changes occur early in tumour development is unclear. Here, the authors analyse methylation events in breast cancer and adjacent normal pairs, and show that methylation changes in the normal tissue are also found in the tumour, suggesting that some of these events occur early in cancer.
- Andrew E Teschendorff
- , Yang Gao
- & Martin Widschwendter
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Article
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Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types
Genes normally expressed in the testis but aberrantly expressed in cancer are termed cancer testis antigens. In this study, the authors catalogue the expression of these genes in 19 different cancer types and correlate expression with some somatically mutated oncogenes.
- Cheng Wang
- , Yayun Gu
- & Zhibin Hu
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Article
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A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma
Using molecular markers is a useful way to predict the prognosis of cancer patients. Here, Wei et al.describe a five gene methylation signature that can predict the prognosis of renal clear cell cancer and validate its use in multiple patient cohorts.
- Jin-Huan Wei
- , Ahmed Haddad
- & Jun-Hang Luo
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Article
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An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis
Leukaemic stem cells are prevalent in acute myeloid leukemia. Here, Jung and colleagues derive a signature of 71 methylated genes that characterise these stem cells and find multiple HOXAgenes within the signature.
- Namyoung Jung
- , Bo Dai
- & Andrew P. Feinberg
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Article
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D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2
IDH1- and IDH2-mutant cancer cells aberrantly accumulate D2-hydroxyglutarate (D2-HG). Here, Lin et al. find loss-of-function mutations in D2-hydroxyglutarate dehydrogenase (D2HGDH), which converts D2-HG to alpha-ketoglutarate (α-KG), in diffuse large B-cell lymphomas and show that D2HGDH via α-KG regulates the expression and activity of IDH2.
- An-Ping Lin
- , Saman Abbas
- & Ricardo C. T. Aguiar
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Article
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A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells
How anti-helminth and allergic immune responses are initiated is poorly understood. Here the authors show that to trigger these responses, dendritic cells specifically require methyl-CpG-binding domain-2, a protein promoting repressed chromatin state.
- Peter C. Cook
- , Heather Owen
- & Andrew S. MacDonald
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Article
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Epigenomic evolution in diffuse large B-cell lymphomas
The contribution of epigenomic alterations to tumour progression and relapse is not well characterized. Here the authors characterize epigenetic evolution in aggressive B-cell lymphoma and find that epigenomic heterogeneity may not only support and drive the relapse phenotype but also be used to predict lymphoma relapse.
- Heng Pan
- , Yanwen Jiang
- & Olivier Elemento
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NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes
Tumour cells disseminated from the primary tumour can remain dormant for years before initiating metastases. Here Sosa et al.show that the orphan nuclear receptor NR2F1 can be induced by bone marrow cues and by epigenetic drugs to promote quiescence and tumour cell dormancy in several cancer types.
- Maria Soledad Sosa
- , Falguni Parikh
- & Julio A. Aguirre-Ghiso
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An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth
The Sonic hedgehog (Shh) signalling pathway plays important roles during development and its abnormal activation has been implicated in cancer. Here the authors uncover an epigenetic switch in the Shh pathway that involves the PRC2, Jmjd3/Kdm6b and Set1/MLL complexes in regulating signalling induced gene activation.
- Xuanming Shi
- , Zilai Zhang
- & Jiang Wu
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The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes
Proteins involved in epigenetic regulation are frequently mutated in several paediatric cancers. Here, Huether et al.characterize the somatic mutation frequency across 21 paediatric cancer subtypes by sequencing 633 epigenetic genes in over 1,000 tumours; generating a rich data set for investigating epigenetic dysregulation.
- Robert Huether
- , Li Dong
- & James R. Downing
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Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
The effects of genetic variation on DNA methylation patterns are poorly understood. Here, Shi et al.systematically map methylation-quantitative trait loci in lung, breast and kidney tissue to reveal the impact of inherited variation on the human methylome, which also affects cancer risk.
- Jianxin Shi
- , Crystal N. Marconett
- & Maria Teresa Landi
Sequence terminus dependent PCR for site-specific mutation and modification detection