Abstract:
BACKGROUND:The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with modified tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is a canonical chromatin mark of active transcription. Recent studies have suggested that H3K4me3 breadth has an important regulatory role in cell identity. This project examined H3K4me3 breadth at transcription start sites (TSS) in primary monocytes and its association with differential gene transcription in SLE. RESULTS:Integrative analysis was applied to chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data generated from primary monocytes as well as genomic data available in public repositories. Four distinctive H3K4me3 patterns of ChIP-seq peaks were identified at 8399 TSSs. Narrow peaks were highly enriched with genes related to housekeeping functions. The broader peaks with extended H3K4me3 immediately upstream and/or downstream of TSS were associated with immune response genes. Many TSSs had downstream H3K4me3 extended to ~650 bp, where the transition of H3K4me3 to H3K36me3, a transcriptional elongation mark, is often found. The H3K4me3 pattern was strongly associated with transcription in SLE. Genes with narrow peaks were less likely (OR = 0.14, p = 2 × 10(-4)) while genes with extended downstream H3K4me3 were more likely (OR = 2.37, p = 1 × 10(-11)) to be overexpressed in SLE. Of the genes significantly overexpressed in SLE, 78.8 % had increased downstream H3K4me3 while only 47.1 % had increased upstream H3K4me3. Gene transcription sensitively and consistently responded to H3K4me3 change downstream of TSSs. Every 1 % increase of H3K4me3 in this region leads to ~1.5 % average increase of transcription. CONCLUSIONS:We identified the immediate TSS downstream nucleosome as a crucial regulator responsible for transcription changes in SLE. This study applied a unique method to study the effect of H3K4me3 breadth on diseases and revealed new insights about epigenetic modifications in SLE, which could lead to novel treatments.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Zhang Z,Shi L,Dawany N,Kelsen J,Petri MA,Sullivan KEdoi
10.1186/s13148-016-0179-4subject
Has Abstractpub_date
2016-02-02 00:00:00pages
14eissn
1868-7075issn
1868-7083pii
179journal_volume
8pub_type
杂志文章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: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:Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0076-2
更新日期:2015-04-10 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 have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whet...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0798-7
更新日期:2020-01-13 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:: 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...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-4-2
更新日期:2012-01-30 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:Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory di...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0561-5
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:The introduction of pathology tissue-chromatin immunoprecipitation (PAT-ChIP), a technique allowing chromatin immunoprecipitation (ChIP) from formalin-fixed paraffin-embedded (FFPE) tissues, has extended the application of chromatin studies to clinical patient samples. However, extensive crosslinking introdu...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0576-y
更新日期:2018-11-16 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:Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next-generation sequencing in representative...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0195-4
更新日期:2016-03-15 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: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: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
abstract:BACKGROUND:Epigenetic mechanisms are thought to be critical in mediating the role of the intrauterine environment on lifelong health and disease. Twin-twin transfusion syndrome (TTTS) is a rare condition wherein fetuses share the placenta and develop vascular anastomoses, which allow blood to flow between the fetuses. ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-18
更新日期:2013-10-03 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: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::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: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: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:The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in vivo.Genome-wide DNA methylation was assessed using a MeDIP-chip analysis. All methylated DNA immunoprecipit...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-6-1
更新日期:2014-01-02 00:00:00
abstract:BACKGROUND:The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein-Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of E...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00989-0
更新日期:2021-01-29 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: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:BACKGROUND:Normal-weight polycystic ovary syndrome (PCOS) women exhibit adipose resistance in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with accelerated lipid accumulation per cell in vitro. The present study examines chromatin accessibility, RNA expressi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00970-x
更新日期:2020-11-23 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: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
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: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