Regulation of telomeric function by DNA methylation differs between humans and mice

Area of Science:

• Epigenetics
• Genomics
• RNA biology

Background:

• Human subtelomeres contain CpG-rich TERRA promoters.
• DNMT3B disruption in humans causes subtelomeric hypomethylation, TERRA upregulation, and telomere shortening.

Purpose of the Study:

• To investigate if DNMT3B regulation of subtelomeric epigenetics is conserved in mice.
• To compare subtelomeric characteristics and TERRA expression between humans and mice.

Main Methods:

• DNA sequence analysis of murine subtelomeres.
• TERRA expression analysis in mouse pluripotent stem cells and MEFs.
• Methylation and telomere function analysis in Dnmt3b-deficient mouse models (ICF1 MEFs).

Main Results:

• Murine subtelomeres are CpG-poor and lack human-like TERRA promoters.
• TERRA is expressed in mice, with higher levels in pluripotent stem cells, but not explained by CpG island methylation.
• Dnmt3b deficiency in mice did not alter subtelomeric methylation, TERRA expression, or telomere length.

Conclusions:

• Murine subtelomere epigenetic characteristics differ significantly from human subtelomeres.
• TERRA transcription in mice is regulated by factors independent of Dnmt3b.