A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Cui, Xiaolong; Nie, Ji; Ku, Jeremy; Dougherty, Urszula; West-Szymanski, Diana C.; Collin, François; Ellison, Christopher K.; Sieh, Laura; Ning, Yuhong; Deng, Zifeng; Zhao, Carolyn W. T.; Bergamaschi, Anna; Pekow, Joel; Wei, Jiangbo; Beadell, Alana V.; Zhang, Zhou; Sharma, Geeta; Talwar, Raman; Arensdorf, Patrick; Karpus, Jason; Goel, Ajay; Bissonnette, Marc; Zhang, Wei; Levy, Samuel; He, Chuan

doi:10.1038/s41467-020-20001-w

Cited by 105 publications

(107 citation statements)

References 40 publications

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“…Unlike 5mC which is recognized for its role in repressing not only protein-coding genes but also a vast amount of transposons in the human genome 6 , 5hmC modifications are associated with active gene regulation 7 . A recent study of a 5hmC map of human tissues showed that 5hmC is enriched preferentially in tissue-specific gene bodies and enhancers 8 , representing a distinct genome-wide distribution from 5mC. Global and focal differential 5hmC modifications have been observed in several cancers, including hematological malignancies 9 .…”

Section: Introductionmentioning

confidence: 99%

Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

et al. 2021

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The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.

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Section: Introductionmentioning

confidence: 99%

Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

et al. 2021

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“…To evaluate 5hmC global changes, we then illustrated 5hmC distributions along gene bodies (± 3 kb), which were similar to those of human adults 17,25 (Fig. 1c).…”

Section: Resultsmentioning

confidence: 95%

“…This phenomenon depends on TET3 activity and the de ciency of zygotic DNMT3A and DNMT1 24 . Although the regulatory power and plasticity of 5hmC have been revealed in human adults 20,25 , its function and reprogramming are still unclear during human foetal organ development after implantation.…”

Section: Introductionmentioning

confidence: 99%

The synergistic coordination of DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine regulates human foetal development

Han¹,

Guo²,

Meng-ke³

et al. 2021

Preprint

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After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, Nano-hmC-Seal and RNA bisulfite sequencing (RNA-BisSeq) were performed and the first multilayer landscapes of both DNA 5hmC and RNA m5C epigenome, as well as the accompanying transcriptome were obtained, in the heart, kidney, liver and lung of the human foetuses at 13 − 28 weeks with 123 samples in total. DNA 5hmC plays a consistently leading role, while RNA m5C acts as a dynamic downstream regulatory valve in regulating gene expression with a turning point of 18–19 weeks. Although, these modifications appear to coordinate in general, they also play different roles with regard to specific functions. Our integrated studies illustrate the epigenetic maps during different stages of human foetal organogenesis, which provide a foundation for understanding the in-depth epigenetic mechanisms for early development and birth defects.

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“…In some of them, we observe the opposite process [ 86 ]. In addition, the methylation level of both individual genes and the general level is tissue and individually specific [ 95 , 96 , 97 ]. The progress in the study of the dependence of the methylation degree of specific loci in the genome on the chronological and biological variation allows for the assumption that in the future it will be possible to develop models predicting the life expectancy and biological age of a human based on the methylation degree of specific loci in selected tissues [ 98 , 99 , 100 , 101 ].…”

Section: Organismal Ageingmentioning

confidence: 99%

Molecular Aspects of Senescence and Organismal Ageing—DNA Damage Response, Telomeres, Inflammation and Chromatin

Sławińska¹,

Krupa²

2021

IJMS

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Cells can become senescent in response to stress. Senescence is a process characterised by a stable proliferative arrest. Sometimes it can be beneficial—for example, it can suppress tumour development or take part in tissue repair. On the other hand, studies show that it is also involved in the ageing process. DNA damage response (DDR) is triggered by DNA damage or telomere shortening during cell division. When left unresolved, it may lead to the activation of senescence. Senescent cells secrete certain proteins in larger quantities. This phenomenon is referred to as senescence-associated secretory phenotype (SASP). SASP can induce senescence in other cells; evidence suggests that overabundance of senescent cells contributes to ageing. SASP proteins include proinflammatory cytokines and metalloproteinases, which degrade the extracellular matrix. Shortening of telomeres is another feature associated with organismal ageing. Older organisms have shorter telomeres. Restoring telomerase activity in mice not only slowed but also partially reversed the symptoms of ageing. Changes in chromatin structure during senescence include heterochromatin formation or decondensation and loss of H1 histones. During organismal ageing, cells can experience heterochromatin loss, DNA demethylation and global histone loss. Cellular and organismal ageing are both complex processes with many aspects that are often related. The purpose of this review is to bring some of these aspects forward and provide details regarding them.

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A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Cited by 105 publications

References 40 publications

Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

The synergistic coordination of DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine regulates human foetal development

Molecular Aspects of Senescence and Organismal Ageing—DNA Damage Response, Telomeres, Inflammation and Chromatin

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