Article thumbnail

Epigenetic Repeat-Induced Gene Silencing in the Chromosomal and Extrachromosomal Contexts in Human Cells.

By Sho-Hei Mitsuda and Noriaki Shimizu

Abstract

A plasmid bearing both a replication initiation region and a matrix attachment region is spontaneously amplified in transfected mammalian cells and generates plasmid repeats in the extrachromosomal double minutes (DMs) or the chromosomal homogeneously staining region (HSR). Generally, the repeat sequences are subject to repeat-induced gene silencing, the mechanism of which remains to be elucidated. Previous research showed that gene expression from the same plasmid repeat was higher from repeats located at DMs than at the HSR, which may reflect the extrachromosomal environment of the DMs. In the current study, plasmid repeats in both DMs and HSR were associated with repressive histone modifications (H3K9me3, H3K9me2), and the levels of repressive chromatin markers were higher in HSR than in DMs. Inactive chromatin is known to spread to neighboring regions in chromosome arm. Here, we found that such spreading also occurs in extrachromosomal DMs. Higher levels of active histone modifications (H3K9Ac, H3K4me3, and H3K79me2) were detected at plasmid repeats in DMs than in HSR. The level of DNA CpG methylation was generally low in both DMs and HSR; however, there were some hypermethylated copies within the population of repeated sequences, and the frequency of such copies was higher in DMs than in HSR. Together, these data suggest a "DNA methylation-core and chromatin-spread" model for repeat-induced gene silencing. The unique histone modifications at the extrachromosomal context are discussed with regard to the model

Topics: Medicine, R, Science, Q
Publisher: Public Library of Science (PLoS)
DOI identifier: 10.1371/journal.pone.0161288
OAI identifier: oai:doaj.org/article:cc6d3a3154e24edfaa948adc6202548d
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://doaj.org/toc/1932-6203 (external link)
  • http://europepmc.org/articles/... (external link)
  • https://doaj.org/article/cc6d3... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.