Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker

Georgina E. T. Blake, Xiaohui Zhao, Hong wa Yung, Graham J. Burton, Anne C. Ferguson-Smith, Russell S. Hamilton and Erica D. Watson ()
Additional contact information
Georgina E. T. Blake: University of Cambridge
Xiaohui Zhao: University of Cambridge
Hong wa Yung: University of Cambridge
Graham J. Burton: University of Cambridge
Anne C. Ferguson-Smith: University of Cambridge
Russell S. Hamilton: University of Cambridge
Erica D. Watson: University of Cambridge

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability in the Mtrr model and genome-wide differential DNA methylation in the germline of Mtrr mutant maternal grandfathers. We observe that, while epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional changes that correlate with germline methylation defects. One region encompasses the Hira gene, which is misexpressed in embryos for at least three wildtype generations in a manner that distinguishes Hira transcript expression as a biomarker of maternal phenotypic inheritance.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24036-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24036-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24036-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().