Abstract:
BACKGROUND:Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog 1 (MLH1) gene. To better understand the role of nucleosomes in splicing, we used MLH1 splice site mutations in Lynch syndrome cases as a model to investigate if abnormal splicing was associated with altered nucleosome positioning at exon-intron boundaries. FINDINGS:Nucleosome Occupancy and Methylome sequencing (NOMe-seq) was used to determine the allele-specific positioning of nucleosomes around heterozygous splice site mutations in lymphoblastoid cells lines (LCLs) derived from six Lynch syndrome patients. These mutations were previously shown to cause exon skipping in five of the six patients. Allele-specific high-resolution nucleosome mapping across exons and exon-intron boundaries revealed high levels of nucleosomes across all regions examined. Alleles containing donor or acceptor splice site mutations showed no consistent alteration in nucleosome positioning or occupancy. CONCLUSION:Nucleosomes were enriched at MLH1 exons in LCLs derived from Lynch syndrome patients, and in this model system the positioning of nucleosomes was unaltered at exon-intron boundaries containing splice site mutations. Thus, these splice site mutations alone do not significantly change the local organisation of nucleosomes.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Sloane MA,Hesson LB,Nunez AC,Thompson BA,Ward RLdoi
10.1186/s13148-014-0032-6subject
Has Abstractpub_date
2014-12-13 00:00:00pages
32issue
1eissn
1868-7075issn
1868-7083pii
32journal_volume
6pub_type
杂志文章abstract::Interleukin 1 and its receptors are associated with allergic diseases such as asthma. In the present study, we measured DNA methylation at the IL1R1 and IL1R2 gene loci and assessed for associations with asthma-related phenotypes and gene expressions. We found that asthmatic and atopic individuals have higher IL1R2 pr...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0114-0
更新日期:2015-08-05 00:00:00
abstract:INTRODUCTION:DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMTs). In cancer cells, global hypomethylation of the genome as a whole and regional hypermethylation...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-7
更新日期:2013-05-02 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::The study of DNA methylation in development and disease has 'exploded' as a field in recent years, with three major classes of measurement now routine. These encompass (i) locus-specific, (ii) genome-scale/wide and (iii) 'global' methylation approaches. Measures of global methylation refer to the level of 5-methylcyto...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0311-0
更新日期:2017-01-13 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: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:Preeclampsia, a pregnancy complication of placental origin is associated with altered expression of angiogenic factors and their receptors. Recently, there is considerable interest in understanding the role of adverse intrauterine conditions in placental dysfunction and adverse pregnancy outcomes. Since we h...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-6
更新日期:2013-04-26 00:00:00
abstract:BACKGROUND:Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00851-3
更新日期:2020-04-21 00:00:00
abstract::Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0046-2
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Aging is a complex phenomenon and characterized by a progressive decline in physiology and function of adult tissues. However, it hasn't been well established of the correlation between aging and global DNA methylation and hydroxymethylation that regulate the growth and development of higher organisms. RESU...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0109-x
更新日期:2015-07-23 00:00:00
abstract:BACKGROUND:Insufficient specificity of the high-risk human papillomavirus (hrHPV) assay in primary cervical cancer screening results in unnecessary referral. Additional assays to triage hrHPV-positive women are needed to improve molecular cervical cancer screening. DNA methylation is a promising biomarker in cervical c...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0122-0
更新日期:2015-08-21 00:00:00
abstract:BACKGROUND:Human 15q11-13 is responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and includes several imprinted genes together with bipartite elements named AS-IC (imprinting center) and PWS-IC. These concertedly confer allele specificity on 15q11-13. Here, we report DNA methylation status of 15q11-1...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0633-1
更新日期:2019-02-28 00:00:00
abstract::Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0525-9
更新日期:2018-07-13 00:00:00
abstract::Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychos...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0038-2
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00997-0
更新日期:2021-01-25 00:00:00
abstract:BACKGROUND:Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagn...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-016-0286-2
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylat...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-021-01017-5
更新日期:2021-01-30 00:00:00
abstract:BACKGROUND:Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00903-8
更新日期:2020-07-27 00:00:00
abstract:BACKGROUND:Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1-/- mice compared with controls. However, little is known of the molecul...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00832-6
更新日期:2020-03-02 00:00:00
abstract:Background:Staging and pathological grading systems are convenient but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Identifying biomarkers for HNSCC that will progress and cause death is a critical research area, particularly if the biomarker can be linked to selection of patient...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0485-0
更新日期:2018-04-11 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study ...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-019-0642-0
更新日期:2019-03-15 00:00:00
abstract:BACKGROUND:ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methyl...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0658-5
更新日期:2019-04-27 00:00:00
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:Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimate...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0174-9
更新日期:2016-01-22 00:00:00
abstract::[This corrects the article DOI: 10.1186/s13148-016-0190-9.]. ...
journal_title:Clinical epigenetics
pub_type: 已发布勘误
doi:10.1186/s13148-016-0250-1
更新日期:2016-08-04 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:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, including DNA methylation, have the potential to mediate the interaction...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0464-5
更新日期:2018-03-05 00:00:00
abstract:BACKGROUND:Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed t...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0693-2
更新日期:2019-07-09 00:00:00
abstract:Background:Maternal social environmental stressors during pregnancy are associated with adverse birth and child developmental outcomes, and epigenetics has been proposed as a possible mechanism for such relationships. Methods:In a Mexican-American birth cohort of 241 maternal-infant pairs, cord blood samples were meas...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0494-z
更新日期:2018-05-08 00:00:00
abstract:Background:Vitamin D deficiency and insufficiency have been established to be strongly associated with increased overall mortality and deaths from specific aging-related diseases. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at the 10 most prominent mortality-related cytosine...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0515-y
更新日期:2018-06-20 00:00:00