Regulation of telomeric function by DNA methylation differs between humans and mice.
Hum Mol Genet
; 29(19): 3197-3210, 2020 11 25.
Article
em En
| MEDLINE
| ID: mdl-32916696
ABSTRACT
The most distal 2 kb region in the majority of human subtelomeres contains CpG-rich promoters for TERRA, a long non-coding RNA. When the function of the de novo DNA methyltransferase DNMT3B is disrupted, as in ICF1 syndrome, subtelomeres are abnormally hypomethylated, subtelomeric heterochromatin acquires open chromatin characteristics, TERRA is highly expressed, and telomeres shorten rapidly. In this study, we explored whether the regulation of subtelomeric epigenetic characteristics by DNMT3B is conserved between humans and mice. Studying the DNA sequence of the distal 30 kb of the majority of murine q-arm subtelomeres indicated that these regions are relatively CpG-poor and do not contain TERRA promoters similar to those present in humans. Despite the lack of human-like TERRA promoters, we clearly detected TERRA expression originating from at least seven q-arm subtelomeres, and at higher levels in mouse pluripotent stem cells in comparison with mouse embryonic fibroblasts (MEFs). However, these differences in TERRA expression could not be explained by differential methylation of CpG islands present in the TERRA-expressing murine subtelomeres. To determine whether Dnmt3b regulates the expression of TERRA in mice, we characterized subtelomeric methylation and associated telomeric functions in cells derived from ICF1 model mice. Littermate-derived WT and ICF1 MEFs demonstrated no significant differences in subtelomeric DNA methylation, chromatin modifications, TERRA expression levels, telomere sister chromatid exchange or telomere length. We conclude that the epigenetic characteristics of murine subtelomeres differ substantially from their human counterparts and that TERRA transcription in mice is regulated by factors others than Dnmt3b.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Telômero
/
Metilação de DNA
/
DNA (Citosina-5-)-Metiltransferases
/
Proteínas de Ligação a DNA
/
Face
/
Fibroblastos
/
Doenças da Imunodeficiência Primária
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Israel