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 methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. RESULTS:Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3' portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. CONCLUSIONS:These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3' portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3' portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Danoff JS,Wroblewski KL,Graves AJ,Quinn GC,Perkeybile AM,Kenkel WM,Lillard TS,Parikh HI,Golino HF,Gregory SG,Carter CS,Bales KL,Connelly JJdoi
10.1186/s13148-021-01017-5subject
Has Abstractpub_date
2021-01-30 00:00:00pages
23issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-021-01017-5journal_volume
13pub_type
杂志文章abstract::Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RR...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0446-7
更新日期:2018-01-25 00:00:00
abstract:BACKGROUND:Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) re...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0341-7
更新日期:2017-04-24 00:00:00
abstract:BACKGROUND:Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues. METHODS:Here, we studied the change of histone modifications in MMTV-PyVT breast ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0645-x
更新日期:2019-03-12 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:The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0073-5
更新日期:2015-04-02 00:00:00
abstract:BACKGROUND:Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD) by 44% and in diabetic CVD patients by 57% on top of statins. A phase III trial, BETonM...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0696-z
更新日期:2019-07-12 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: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: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: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: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::Duchenne muscular dystrophy (DMD) is a multisystemic disorder that affects 1:5000 boys. The severity of the phenotype varies dependent on the mutation site in the DMD gene and the resultant dystrophin expression profile. In skeletal muscle, dystrophin loss is associated with the disintegration of myofibers and their i...
journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
doi:10.1186/s13148-021-01001-z
更新日期:2021-01-19 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: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: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:Hypericin-mediated photodynamic therapy (HY-PDT) has recently captured increased attention as an alternative minimally invasive anticancer treatment, although cancer cells may acquire resistance. Therefore, combination treatments may be necessary to enhance HY-PDT efficacy. Histone deacetylase inhibitors (HD...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0359-x
更新日期:2017-06-08 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:Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental heal...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0416-5
更新日期:2017-10-23 00:00:00
abstract:Background:Reduced expression of retinoic acid-induced 2 (RAI2) was found in breast cancer. The regulation and function of RAI2 in human colorectal cancer (CRC) remain unclear. Methods:Eight CRC cell lines and 237 cases of primary CRC were analyzed. Methylation-specific PCR (MSP), flow cytometry, xenograft mouse model...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0501-4
更新日期:2018-05-23 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: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:BACKGROUND:Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0784-0
更新日期:2019-12-10 00:00:00
abstract:BACKGROUND:Most research into myocardial infarctions (MIs) have focused on preventative efforts. For survivors, the occurrence of an MI represents a major clinical event that can have long-lasting consequences. There has been little to no research into the molecular changes that can occur as a result of an incident MI....
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0588-7
更新日期:2018-12-27 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: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::Lymphocytes from the peripheral blood of patients with prostate cancer-the most frequent (noncutaneous) tumor in men-display epigenetic aberrations (altered modes of allelic replication) characteristic of the malignant phenotype. The present study aims to determine whether replication aberrations add certainty to the ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0029-3
更新日期:2011-08-01 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::In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methyla...
journal_title:Clinical epigenetics
pub_type: 信件
doi:10.1186/s13148-017-0402-y
更新日期:2017-09-15 00:00:00
abstract:BACKGROUND:The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown. METHOD:We checked the expression of Snail2 in several clinical CRC specimens. Then, we established...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0592-y
更新日期:2018-12-12 00:00:00
abstract:BACKGROUND:Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adip...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0567-z
更新日期:2018-10-24 00:00:00