Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3
Romain O. Georges,
Hugo Sepulveda,
J. Carlos Angel,
Eric Johnson,
Susan Palomino,
Roberta B. Nowak,
Arshad Desai,
Isaac F. López-Moyado and
Anjana Rao ()
Additional contact information
Romain O. Georges: La Jolla Institute for Immunology
Hugo Sepulveda: La Jolla Institute for Immunology
J. Carlos Angel: La Jolla Institute for Immunology
Eric Johnson: La Jolla Institute for Immunology
Susan Palomino: La Jolla Institute for Immunology
Roberta B. Nowak: La Jolla Institute for Immunology
Arshad Desai: University of California, San Diego
Isaac F. López-Moyado: La Jolla Institute for Immunology
Anjana Rao: La Jolla Institute for Immunology
Nature Communications, 2022, vol. 13, issue 1, 1-15
Abstract:
Abstract TET (Ten-Eleven Translocation) dioxygenases effect DNA demethylation through successive oxidation of the methyl group of 5-methylcytosine (5mC) in DNA. In humans and in mouse models, TET loss-of-function has been linked to DNA damage, genome instability and oncogenesis. Here we show that acute deletion of all three Tet genes, after brief exposure of triple-floxed, Cre-ERT2-expressing mouse embryonic stem cells (mESC) to 4-hydroxytamoxifen, results in chromosome mis-segregation and aneuploidy; moreover, embryos lacking all three TET proteins showed striking variation in blastomere numbers and nuclear morphology at the 8-cell stage. Transcriptional profiling revealed that mRNA encoding a KH-domain protein, Khdc3 (Filia), was downregulated in triple TET-deficient mESC, concomitantly with increased methylation of CpG dinucleotides in the vicinity of the Khdc3 gene. Restoring KHDC3 levels in triple Tet-deficient mESC prevented aneuploidy. Thus, TET proteins regulate Khdc3 gene expression, and TET deficiency results in mitotic infidelity and genome instability in mESC at least partly through decreased expression of KHDC3.
Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/s41467-022-33742-7 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:13:y:2022:i:1:d:10.1038_s41467-022-33742-7
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-022-33742-7
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 ().