Concomitant downregulation of the imprinted genes DLK1 and MEG3 at 14q32.2 by epigenetic mechanisms in urothelial carcinoma

Clinical Epigenetics
Annemarie GreifeWolfgang A Schulz

Abstract

The two oppositely imprinted and expressed genes, DLK1 and MEG3, are located in the same gene cluster at 14q32. Previous studies in bladder cancer have suggested that tumor suppressor genes are located in this region, but these have not been identified. We observed that both DLK1 and MEG3 are frequently silenced in urothelial cancer tissues and cell lines. The concomitant downregulation of the two genes is difficult to explain by known mechanisms for inactivating imprinted genes, namely deletion of active alleles or epitype switching. Indeed, quantitative PCR revealed more frequent copy number gains than losses in the gene cluster that were, moreover, consistent within each sample, excluding gene losses as the cause of downregulation. Instead, we observed distinctive epigenetic alterations at the three regions controlling DLK1 and MEG3 expression, namely the DLK1 promoter; the intergenic (IG) and MEG3 differentially methylated regions (DMRs). Bisulfite sequencing and pyrosequencing revealed novel patterns of DNA methylation in tumor cells, which were distinct from that of either paternal allele. Furthermore, chromatin immunoprecipitation demonstrated loss of active and gain of repressive histone modifications at all regulatory ...Continue Reading

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Citations

Sep 15, 2016·Epigenomics·Wolfgang A Schulz, Wolfgang Goering
Nov 23, 2017·Genes·Caterina GulìaRoberto Piergentili
Dec 10, 2017·Biophysics Reviews·Mohammad TaheriSoudeh Ghafouri-Fard
Aug 4, 2018·Biotechnology & Genetic Engineering Reviews·Aras RafieeFatemeh Nuri
Jan 25, 2019·Journal of Cellular Physiology·Mohammad AminiMehdi Manoochehri
Oct 27, 2017·Oncotarget·Yuqing HeWeiming He
Apr 29, 2016·Briefings in Functional Genomics·Mojdeh Nasrollahzadeh-KhakianiParvaneh Nikpour
Jun 3, 2021·Genes·Lilla KrokkerHenriett Butz
Nov 10, 2020·Life Sciences·Md Nazim Uddin, Xiaosheng Wang

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Methods Mentioned

BETA
immunoprecipitation
ChIP
PCR

Software Mentioned

UCSC genome browser
SPSS

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