Genome-wide analysis reveals no evidence of trans chromosomal regulation of mammalian immune development

PLoS Genet. 2018 Jun 8;14(6):e1007431. doi: 10.1371/journal.pgen.1007431. eCollection 2018 Jun.

Abstract

It has been proposed that interactions between mammalian chromosomes, or transchromosomal interactions (also known as kissing chromosomes), regulate gene expression and cell fate determination. Here we aimed to identify novel transchromosomal interactions in immune cells by high-resolution genome-wide chromosome conformation capture. Although we readily identified stable interactions in cis, and also between centromeres and telomeres on different chromosomes, surprisingly we identified no gene regulatory transchromosomal interactions in either mouse or human cells, including previously described interactions. We suggest that advances in the chromosome conformation capture technique and the unbiased nature of this approach allow more reliable capture of interactions between chromosomes than previous methods. Overall our findings suggest that stable transchromosomal interactions that regulate gene expression are not present in mammalian immune cells and that lineage identity is governed by cis, not trans chromosomal interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomes, Mammalian / chemistry
  • Chromosomes, Mammalian / genetics*
  • Chromosomes, Mammalian / metabolism
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • Flow Cytometry
  • Gene Expression Regulation*
  • Genome
  • Humans
  • Immunity, Cellular / genetics*
  • Male
  • Mammals / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nucleic Acid Conformation
  • Stereoisomerism

Substances

  • Chromatin
  • DNA

Grants and funding

This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (GKS #1058892, LCH and NGB #1037321, #1129033, #1080887, ATLL and GKS #1054618, RSA and TMJ #1049307, #1100451, TMJ #1124081) and the Australian Research Council (RSA #130100541). This study was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.