Faculty Opinions recommendation of FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription.

2008 ◽  
Author(s):  
Andrew D Sharrocks
Keyword(s):  
Epigenetic Signatures

scholarly journals Distinct epigenetic signatures between adult-onset and late-onset depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Yamagata ◽  
Hiroyuki Ogihara ◽  
Koji Matsuo ◽  
Shusaku Uchida ◽  
Ayumi Kobayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Adult Onset ◽  
Blood Biomarkers ◽  
Major Depressive ◽  
Genome Wide ◽  
Healthy Control ◽  
Epigenetic Signatures

AbstractThe heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.

scholarly journals Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming

2021 ◽  
Vol 7 (15) ◽  
pp. eabe8978
Author(s):  
Álvaro Herrero-Navarro ◽  
Lorenzo Puche-Aroca ◽  
Verónica Moreno-Juan ◽  
Alejandro Sempere-Ferràndez ◽  
Ana Espinosa ◽  
...  
Keyword(s):  
Molecular Diversity ◽  
Regional Identity ◽  
Brain Regions ◽  
Molecular Signature ◽  
Specific Gene ◽  
Thalamic Nuclei ◽  
Brain Repair ◽  
Cell Diversity ◽  
Regional Specificity ◽  
Epigenetic Signatures

Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.

scholarly journals Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongzheng Li ◽  
Boxin Xue ◽  
Mengling Zhang ◽  
Liwei Zhang ◽  
Yingping Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Structural Dynamics ◽  
Replication Origin ◽  
High Efficiency ◽  
S Phase ◽  
Chromatin Domain ◽  
Replication Origins ◽  
Replication Efficiency ◽  
Topologically Associating Domains ◽  
Epigenetic Signatures

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

scholarly journals H3K27 modifiers regulate lifespan in C. elegans in a context-dependent manner

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abigail R. R. Guillermo ◽  
Karolina Chocian ◽  
Gavriil Gavriilidis ◽  
Julien Vandamme ◽  
Anna Elisabetta Salcini ◽  
...  
Keyword(s):  
Lifespan Extension ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Animal Cells ◽  
C Elegans ◽  
Specific Effects ◽  
Aberrant Gene Expression ◽  
Lysine Methyltransferase ◽  
Epigenetic Signatures ◽  
Aberrant Gene

Abstract Background Evidence of global heterochromatin decay and aberrant gene expression in models of physiological and premature ageing have long supported the “heterochromatin loss theory of ageing”, which proposes that ageing is aetiologically linked to, and accompanied by, a progressive, generalised loss of repressive epigenetic signatures. However, the remarkable plasticity of chromatin conformation suggests that the re-establishment of such marks could potentially revert the transcriptomic architecture of animal cells to a “younger” state, promoting longevity and healthspan. To expand our understanding of the ageing process and its connection to chromatin biology, we screened an RNAi library of chromatin-associated factors for increased longevity phenotypes. Results We identified the lysine demethylases jmjd-3.2 and utx-1, as well as the lysine methyltransferase mes-2 as regulators of both lifespan and healthspan in C. elegans. Strikingly, we found that both overexpression and loss of function of jmjd-3.2 and utx-1 are all associated with enhanced longevity. Furthermore, we showed that the catalytic activity of UTX-1, but not JMJD-3.2, is critical for lifespan extension in the context of overexpression. In attempting to reconcile the improved longevity associated with both loss and gain of function of utx-1, we investigated the alternative lifespan pathways and tissue specificity of longevity outcomes. We demonstrated that lifespan extension caused by loss of utx-1 function is daf-16 dependent, while overexpression effects are partially independent of daf-16. In addition, lifespan extension was observed when utx-1 was knocked down or overexpressed in neurons and intestine, whereas in the epidermis, only knockdown of utx-1 conferred improved longevity. Conclusions We show that the regulation of longevity by chromatin modifiers can be the result of the interaction between distinct factors, such as the level and tissue of expression. Overall, we suggest that the heterochromatin loss model of ageing may be too simplistic an explanation of organismal ageing when molecular and tissue-specific effects are taken into account.

scholarly journals Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Caterina Strisciuglio ◽  
Felicity Payne ◽  
Komal Nayak ◽  
Marialuisa Andreozzi ◽  
Alessandra Vitale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Eosinophilic Esophagitis ◽  
Field Potential ◽  
Line Treatment ◽  
Food Impaction ◽  
First Line ◽  
Genome Wide ◽  
Epigenetic Signatures ◽  
The Impact ◽  
First Line Treatment

AbstractEosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers.

scholarly journals Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis

Oncotarget ◽  
2014 ◽  
Vol 5 (19) ◽  
pp. 9425-9443 ◽  
Author(s):  
Ryan A. Hlady ◽  
Rochelle L. Tiedemann ◽  
William Puszyk ◽  
Ivan Zendejas ◽  
Lewis R. Roberts ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Hepatitis Infection ◽  
Epigenetic Signatures

scholarly journals Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants’ temperament at 3 months

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Livio Provenzi ◽  
Fabiana Mambretti ◽  
Marco Villa ◽  
Serena Grumi ◽  
Andrea Citterio ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Collective Trauma ◽  
Transporter Gene ◽  
Stress Exposure ◽  
Buccal Cells ◽  
Stress Effects ◽  
Cpg Sites ◽  
Stress Related Genes ◽  
Related Stress ◽  
Epigenetic Signatures

AbstractThe COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants’ temperament at 3 months.

scholarly journals Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice

Blood ◽  
2017 ◽  
Vol 129 (19) ◽  
pp. 2645-2656 ◽  
Author(s):  
Idoia García-Ramírez ◽  
Saber Tadros ◽  
Inés González-Herrero ◽  
Alberto Martín-Lorenzo ◽  
Guillermo Rodríguez-Hernández ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Disease Etiology ◽  
Key Points ◽  
Epigenetic Signatures

Key Points Crebbp inactivation perturbs B-cell development, but cooperates with Bcl2 overexpression to promote lymphoma. Transcriptional and epigenetic signatures of Crebbp loss implicate Myc in disease etiology.

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