RRC ID 80698
Author Matsuzaki H, Kimura M, Morihashi M, Tanimoto K.
Title Imprinted DNA methylation of the H19 ICR is established and maintained in vivo in the absence of Kaiso.
Journal Epigenetics Chromatin
Abstract BACKGROUND:Paternal allele-specific DNA methylation of the imprinting control region (H19 ICR) controls genomic imprinting at the Igf2/H19 locus. We previously demonstrated that the mouse H19 ICR transgene acquires imprinted DNA methylation in preimplantation mouse embryos. This activity is also present in the endogenous H19 ICR and protects it from genome-wide reprogramming after fertilization. We also identified a 118-bp sequence within the H19 ICR that is responsible for post-fertilization imprinted methylation. Two mutations, one in the five RCTG motifs and the other a 36-bp deletion both in the 118-bp segment, caused complete and partial loss, respectively, of methylation following paternal transmission in each transgenic mouse. Interestingly, these mutations overlap with the binding site for the transcription factor Kaiso, which is reportedly involved in maintaining paternal methylation at the human H19 ICR (IC1) in cultured cells. In this study, we investigated if Kaiso regulates imprinted DNA methylation of the H19 ICR in vivo.
RESULTS:Neither Kaiso deletion nor mutation of Kaiso binding sites in the 118-bp region affected DNA methylation of the mouse H19 ICR transgene. The endogenous mouse H19 ICR was methylated in a wild-type manner in Kaiso-null mutant mice. Additionally, the human IC1 transgene acquired imprinted DNA methylation after fertilization in the absence of Kaiso.
CONCLUSIONS:Our results indicate that Kaiso is not essential for either post-fertilization imprinted DNA methylation of the transgenic H19 ICR in mouse or for methylation imprinting of the endogenous mouse H19 ICR.
Volume 17(1)
Pages 20
Published 2024-6-5
DOI 10.1186/s13072-024-00544-8
PII 10.1186/s13072-024-00544-8
PMID 38840164
MeSH Animals Binding Sites DNA Methylation* Female Genomic Imprinting* Male Mice Mice, Transgenic RNA, Long Noncoding* / genetics RNA, Long Noncoding* / metabolism Repressor Proteins Transcription Factors* / genetics Transcription Factors* / metabolism
Mice RBRC00639