Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer

نویسندگان

  • Natasha Vafadar-Isfahani
  • Christina Parr
  • Lara E McMillan
  • Juliane Sanner
  • Zhao Yeo
  • Stephen Saddington
  • Oliver Peacock
  • Hazel A Cruickshanks
  • Richard R Meehan
  • Jonathan N Lund
  • Cristina Tufarelli
چکیده

Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Investigating the methylation status of DACT2 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer

Colorectal cancer (CRC) is one of the common causes of cancer death in Iranian population. Both genetic and epigenetic changes have been implicated in CRC pathogenesis. DACT2 gene as one of the WNT signaling pathway inhibitor was shown to display tumor suppressor activity in many cancers. The aim of present study was to investigate the methylation status of DACT2 gene and its ...

متن کامل

O6-Methylguanine-DNA Methyltransferase and ATP-Binding Cassette Membrane Transporter G2 Promotor Methylation: Can Predict the Response to Chemotherapy in Advanced Breast Cancer?

Background: ATP-binding cassette membrane transporter G2 (ABCG2) gene is one of transporter family and well characterized for their association with chemoresistance. Promoter methylation is a mechanism for regulation of gene expression. O6-Methyl guanine DNA methyl transferase (MGMT) gene plays a fundamental role in DNA repair. MGMT has the ability to remove alkyl adducts from DNA at the O6 pos...

متن کامل

Promoter hypermethylation of KLOTHO; an anti-senescence related gene in colorectal cancer patients of Kashmir valley

Hypermethylation of CpG islands located in the promoter regions of genes is a major event in the development of the majority of cancer types, due to the subsequent aberrant silencing of important tumor suppressor genes. KLOTHO; a novel gene associated primarily with suppressing senescence has been shown to contribute to tumorigenesis as a result of its impaired function. Recently the relevance ...

متن کامل

Association between HIC1 and RASSF1A Promoter Hypermethylation with MTHFD1 G1958A Polymorphism and Clinicopathological Features of Breast Cancer in Iranian Patients

Background: Ras-associated domain family 1 (RASSF1A) and hypermethylated in cancer (HIC1) genes are methylated more frequently in breast cancer. Genetic factors that alter the DNA methylation levels in normal and tumor tissues could therefore influence the susceptibility to this tumor phenotype. Objective: We determined the frequency of aberrant methylation of HIC1 and RASSF1A gene promoters an...

متن کامل

Effect of Cold Atmospheric Plasma on Gene Expression and Methylation of Genes Involved in Colorectal Cancer

Background and purpose: Colorectal cancer (CRC) is ranked as the second most common cancer in men and the third most common cancer in women worldwide. Routine treatments have many side effects and little efficiency. The aim of this study was to investigate the effects of Cold Atmospheric Plasma (CAP) on epigenetic changes of some genes involved in CRC progression. Materials and methods: Prolif...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 12  شماره 

صفحات  -

تاریخ انتشار 2017