Epigenetics: Definition, Mechanisms and Clinical Perspective

Dupont, Christophe; Armant, D. Randall; Brenner, Carol A.

doi:10.1055/s-0029-1237423

Cited by 606 publications

(467 citation statements)

References 90 publications

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“…Therefore, nongenetic factors, such as epigenetic modifications, may also be causative and currently the subject of intense research. Epigenetics is the study of changes in gene expression and/or chromatin structure and cell function caused by mechanisms other than changes in the underlying DNA sequence (95). This field is an important area of investigation because epigenetic modifications may explain differential regulation of AD risk genes and genomic regions without changes to their DNA sequence and, therefore, undetected in genetic studies.…”

Section: Epigenetic Regulation Of App Regulation Of Alternative App Pmentioning

confidence: 99%

The human β-amyloid precursor protein: biomolecular and epigenetic aspects

Nguyen¹

2015

Biomolecular Concepts

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Beta-amyloid precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. APP plays a central role in Alzheimer's disease (AD) pathogenesis: APP processing generates β-amyloid (Aβ) peptides, which are deposited as amyloid plaques in the brains of AD individuals; point mutations and duplications of APP are causal for a subset of early-onset familial AD (FAD) (onset age < 65 years old). However, these mutations in FAD represent a very small percentage of cases (∼1%). Approximately 99% of AD cases are nonfamilial and late-onset, i.e., sporadic AD (SAD) (onset age > 65 years old), and the pathophysiology of this disorder is not yet fully understood. APP is an extremely complex molecule that may be functionally important in its full-length configuration, as well as the source of numerous fragments with varying effects on neural function, yet the normal function of APP remains largely unknown. This article provides an overview of our current understanding of APP, including its structure, expression patterns, proteolytic processing and putative functions. Importantly, and for the first time, my recent data concerning its epigenetic regulation, especially in alternative APP pre-mRNA splicing and in the control of genomic rearrangements of the APP gene, are also reported. These findings may provide new directions for investigating the role of APP in neuropathology associated with a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt) found in patients with Lesch-Nyhan syndrome (LNS) and its attenuated variants (LNVs). Also, these findings may be of significance for research in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome (FXS) and AD, with its diversity and complexity, SAD in particular. Accurate quantification of various APPmRNA isoforms in brain tissues is needed, and antisense drugs are potential treatments.

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Section: Epigenetic Regulation Of App Regulation Of Alternative App Pmentioning

confidence: 99%

The human β-amyloid precursor protein: biomolecular and epigenetic aspects

Nguyen¹

2015

Biomolecular Concepts

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“…These mechanisms result in heritable changes in gene expression and function without alterations in the DNA sequence itself (47) .…”

Section: Modulation Of Wnt Signalling By Resistant Starch and Butyratmentioning

confidence: 99%

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

2015

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Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

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“…It is the study of changes in gene function that do not include a change in DNA sequence. These modulations have a crucial role in the silencing and expression of noncoding sequences (14) .…”

Section: Discussionmentioning

confidence: 99%

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

Youssef

Ismail²,

Attia³

et al. 2018

The Egyptian Journal of Hospital Medicine

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Background: Acute myeloid leukemia (AML) is a malignant disorder of hematopoietic tissue. It is one of the most common malignancies in adults. It is characterized by its heterogeneous and complex nature that includes chromosomal, genetic and epigenetic abnormalities. MicroRNAs have been described to be one of the epigenetic regulators in AML. Objective: The present study focused on measuring expression levels of miR-9 in de novo AML patients. 30 bone marrow samples were collected from patients attending at Hematology and Oncology Unit of Aldemerdash Hospitals.MiR-9 expression levels were measured using real time PCR. These expression levels were compared to 30 adult healthy volunteers. Patients and Methods: The present study was carried out in medical oncology and Clinical Pathology Departments of Ain Shams University and National Research Centre, Egypt during the period between September 2017 and April 2018. Results: Statistical analysis of the results showed that miR-9 was significantly down regulated in AML patients in comparison to controls. It is also significantly correlated to platelet count. Regarding diagnostic performance, this study showed that miR-9 has weak diagnostic performance but regarding screening function, it has perfect sensitivity but weak specificity so it can be used as an excluding test. Conclusion: This study showed reduction of miR-9 in bone marrow of AML patients and opened the horizon for future studies on diagnostic and screening performance of miR-9 to be performed on larger scale and different ethnic groups.

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Epigenetics: Definition, Mechanisms and Clinical Perspective

Cited by 606 publications

References 90 publications

The human β-amyloid precursor protein: biomolecular and epigenetic aspects

The human β-amyloid precursor protein: biomolecular and epigenetic aspects

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

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