Transvection-like interchromosomal interaction is not observed at the transcriptional level when tested in the Rosa26 locus in mouse

PLoS One. 2019 Feb 14;14(2):e0203099. doi: 10.1371/journal.pone.0203099. eCollection 2019.


Long-range associations between enhancers and their target gene promoters have been shown to play critical roles in executing genome function. Recent variations of chromosome capture technology have revealed a comprehensive view of intra- and interchromosomal contacts between specific genomic sites. The locus control region of the β-globin genes (β-LCR) is a super-enhancer that is capable of activating all of the β-like globin genes within the locus in cis through physical interaction by forming DNA loops. CTCF helps to mediate loop formation between LCR-HS5 and 3'HS1 in the human β-globin locus, in this way thought to contribute to the formation of a "chromatin hub". The β-globin locus is also in close physical proximity to other erythrocyte-specific genes located long distances away on the same chromosome. In this case, erythrocyte-specific genes gather together at a shared "transcription factory" for co-transcription. Theoretically, enhancers could also activate target gene promoters at the identical loci, yet on different chromosomes in trans, a phenomenon originally described as transvection in Drosophilla. Although close physical proximity has been reported for the β-LCR and the β-like globin genes when integrated at the mouse homologous loci in trans, their structural and functional interactions were found to be rare, possibly because of a lack of suitable regulatory elements that might facilitate such trans interactions. Therefore, we re-evaluated presumptive transvection-like enhancer-promoter communication by introducing CTCF binding sites and erythrocyte-specific transcription units into both LCR-enhancer and β-promoter alleles, each inserted into the mouse ROSA26 locus on separate chromosomes. Following cross-mating of mice to place the two mutant loci at the identical chromosomal position and into active chromation in trans, their transcriptional output was evaluated. The results demonstrate that there was no significant functional association between the LCR and the β-globin gene in trans even in this idealized experimental context.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • CCCTC-Binding Factor / metabolism
  • Chromatin / metabolism
  • Chromosomes / genetics
  • Chromosomes / physiology
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic / genetics
  • Female
  • Locus Control Region / genetics
  • Male
  • Mice
  • Promoter Regions, Genetic / genetics
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism*
  • Regulatory Sequences, Nucleic Acid / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics*
  • Transcription, Genetic / physiology
  • beta-Globins / genetics


  • CCCTC-Binding Factor
  • Chromatin
  • Ctcf protein, mouse
  • DNA-Binding Proteins
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • RNA, Untranslated
  • Transcription Factors
  • beta-Globins

Grants and funding

This work was supported in part by research grants from JSPS (Japan Society for the Promotion of Science, KAKENHI Grant Number 26292189 [Grant-in-Aid for Scientific Research (B) to K.T.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.