Abstract:
: Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit is the triplet GAA•TTC and the tandem array is located in the first intron of the frataxin (FXN) gene. Pathology arises because expanded alleles make lower than normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN gene product. The repeats form a variety of unusual DNA structures that have the potential to affect gene expression in a number of ways. For example, triplex formation in vitro and in bacteria leads to the formation of persistent RNA:DNA hybrids that block transcription. In addition, these repeats have been shown to affect splicing in model systems. More recently, it has been shown that the region flanking the repeats in the FXN gene is enriched for epigenetic marks characteristic of transcriptionally repressed regions of the genome. However, exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the subject of much debate. Identifying the mechanism or mechanisms responsible for the FXN mRNA deficit in FRDA is important for the development of treatments for this currently incurable disorder. This review discusses evidence for and against different models for the repeat-mediated mRNA deficit.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Kumari D,Usdin Kdoi
10.1186/1868-7083-4-2subject
Has Abstractpub_date
2012-01-30 00:00:00pages
2issue
1eissn
1868-7075issn
1868-7083pii
1868-7083-4-2journal_volume
4pub_type
杂志文章abstract:BACKGROUND:Mitochondrial dysregulation and aberrant epigenetic mechanisms have been frequently reported in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and several researchers suggested that epigenetic dysregulation in mitochondrial DNA (mtDNA) could contribute to the neurodegenerative pro...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00933-2
更新日期:2020-09-11 00:00:00
abstract:Background:Methylation-associated SOX family genes have been proved to be involved in multiple essential processes during carcinogenesis and act as potential biomarkers for cancer diagnosis, staging, prediction of prognosis, and monitoring of response to therapy. Herein, we revealed SOX30 methylation and its clinical i...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0523-y
更新日期:2018-07-05 00:00:00
abstract:BACKGROUND:In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0794-y
更新日期:2019-12-19 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0185-6
更新日期:2016-02-19 00:00:00
abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00
abstract:BACKGROUND:Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic hea...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0558-0
更新日期:2018-10-20 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (T2D) is highly prevalent in Middle-Eastern and North African Arab populations, but the molecular basis for this susceptibility is unknown. Altered DNA methylation levels were reported in insulin-secreting and responding tissues, but whether methylation in accessible tissues such as ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0069-1
更新日期:2015-03-28 00:00:00
abstract:BACKGROUND:The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race a...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0080-6
更新日期:2015-04-21 00:00:00
abstract:BACKGROUND:The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0063-7
更新日期:2015-03-14 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0152-7
更新日期:2015-11-05 00:00:00
abstract:BACKGROUND:A key focus in cancer research is the discovery of biomarkers that accurately diagnose early lesions in non-invasive tissues. Several studies have identified malignancy-associated DNA methylation changes in blood, yet no general cancer biomarker has been identified to date. Here, we explore the potential of ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0172-y
更新日期:2016-01-20 00:00:00
abstract:BACKGROUND:Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0335-5
更新日期:2017-04-14 00:00:00
abstract:Background:New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HD...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0434-3
更新日期:2018-01-04 00:00:00
abstract:BACKGROUND:Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0072-6
更新日期:2015-03-29 00:00:00
abstract:BACKGROUND:Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have often failed to replicate at the level o...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0705-2
更新日期:2019-10-15 00:00:00
abstract:BACKGROUND:Frozen-thawed embryo transfer (FET) is increasingly available for the improvement of the success rate of assisted reproductive technologies other than fresh embryo transfer (ET). There have been numerous findings that FET provides better obstetric and perinatal outcomes. However, the birth weight of infants ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0379-6
更新日期:2017-08-03 00:00:00
abstract:BACKGROUND:Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which bec...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0377-8
更新日期:2017-08-14 00:00:00
abstract:BACKGROUND:The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigen...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0177-6
更新日期:2016-01-28 00:00:00
abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) is the third most commonly diagnosed human malignancy worldwide. Upregulation of inhibitory immune checkpoints by tumor-infiltrating immune cells (TIICs) or their ligands by tumor cells leads to tumor evasion from host immunosurveillance. Changes in DNA methylation pattern and enrichm...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0539-3
更新日期:2018-08-06 00:00:00
abstract::Heterozygous mutation of the transcription factor HNF1B is the most common cause of monogenetic developmental renal disease. Disease-associated mutations fall into two categories: HNF1B intragenic mutations and a 1.3 Mb deletion at chromosome 17q12. An increase in neurodevelopmental disorders has been observed in indi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0530-z
更新日期:2018-07-18 00:00:00
abstract::Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction p...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-010-0018-y
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neopla...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0559-z
更新日期:2018-10-19 00:00:00
abstract:: Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours rendering them frequently resistant to both radiotherapy and chemotherapy regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven by bot...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-3-9
更新日期:2011-12-05 00:00:00
abstract:BACKGROUND:Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alteratio...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0052-x
更新日期:2015-03-13 00:00:00
abstract:BACKGROUND:The most common sex chromosomal aneuploidy in males is Klinefelter syndrome, which is characterized by at least one supernumerary X chromosome. While these men have long been considered infertile, focal spermatogenesis can be observed in some patients, and sperm can be surgically retrieved and used for artif...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0720-3
更新日期:2019-08-28 00:00:00
abstract:BACKGROUND:The tumor-specific microregional effects of the anticancer agent RRx-001, a novel epigenetic-based radio/chemosensitizer with nitrogen oxide-donating properties in phase II clinical trials, were investigated with whole tissue section quantitative immunohistological staining in mouse SCCVII and human U87 tumo...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0220-7
更新日期:2016-05-11 00:00:00
abstract:BACKGROUND:Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00959-6
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00844-2
更新日期:2020-04-07 00:00:00
abstract:BACKGROUND:Smoking is the largest preventable cause of morbidity and mortality in the United States. In previous work, we demonstrated that altered DNA methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with self-reported smoking in 19-year-old African Americans with relatively low levels of sm...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-19
更新日期:2013-10-11 00:00:00