Active human nucleolar organizer regions are interspersed with inactive rDNA repeats in normal and tumor cells

Zillner, Karina and Komatsu, Jun and Filarsky, Katharina and Kalepu, Rajakiran and Bensimon, Aaron and Nemeth, Attila (2015) Active human nucleolar organizer regions are interspersed with inactive rDNA repeats in normal and tumor cells. EPIGENOMICS, 7 (3). pp. 363-378. ISSN 1750-1911, 1750-192X

Full text not available from this repository. (Request a copy)

Abstract

Aim: The synthesis of rRNA is a key determinant of normal and malignant cell growth and subject to epigenetic regulation. Yet, the epigenomic features of rDNA arrays clustered in nucleolar organizer regions are largely unknown. We set out to explore for the first time how DNA methylation is distributed on individual rDNA arrays. Materials & Methods: Here we combined immunofluorescence detection of DNA modifications with fluorescence hybridization of single DNA fibers, metaphase immuno-FISH and methylation-sensitive restriction enzyme digestions followed by Southern blot. Results: We found clustering of both hypomethylated and hypermethylated repeat units and hypermethylation of noncanonical rDNA in IMR90 fibroblasts and HCT116 colorectal carcinoma cells. Surprisingly, we also found transitions between hypo- and hypermethylated rDNA repeat clusters on single DNA fibers. Conclusion: Collectively, our analyses revealed co-existence of different epialleles on individual nucleolar organizer regions and showed that epi-combing is a valuable approach to analyze epigenomic patterns of repetitive DNA.

Item Type: Article
Uncontrolled Keywords: RIBOSOMAL-RNA GENES; POLYMERASE I TRANSCRIPTION; SINGLE-MOLECULE ANALYSIS; DNA METHYLATION; NANOFLUIDIC CHANNEL; EMERGING TARGET; CANCER; ARCHITECTURE; EPIGENETICS; MECHANISMS; DNA methylation; epigenetics; epigenomics; nucleolar organizer region; nucleolus; ribosomal DNA; single-molecule analysis
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III
Depositing User: Dr. Gernot Deinzer
Date Deposited: 31 Jul 2019 08:20
Last Modified: 31 Jul 2019 08:20
URI: https://pred.uni-regensburg.de/id/eprint/6237

Actions (login required)

View Item View Item