RT Journal Article
SR Electronic
T1 ZMYM2 is essential for methylation of germline genes and active transposons in embryonic development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.13.507699
DO 10.1101/2022.09.13.507699
A1 Adda-Lee Graham-Paquin
A1 Deepak Saini
A1 Jacinthe Sirois
A1 Ishtiaque Hossain
A1 Megan S. Katz
A1 Qinwei Kim-Wee Zhuang
A1 Sin Young Kwon
A1 Yojiro Yamanaka
A1 Guillaume Bourque
A1 Maxime Bouchard
A1 William A. Pastor
YR 2022
UL http://biorxiv.org/content/early/2022/11/18/2022.09.13.507699.abstract
AB ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. Zmym2-/- embryos show ubiquitous overexpression of LINE-1 protein as well as aberrant expression of transposon-gene fusion transcripts. Interaction and colocalization data indicate that ZMYM2 homes to germline genes via binding to the non-canonical polycomb complex PRC1.6 and to transposons via the TRIM28 complex. In the absence of ZMYM2, hypermethylation of histone 3 lysine 4 occurs at target sites, creating a chromatin landscape unfavourable for establishment of DNA methylation. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryonic development.Competing Interest StatementThe authors have declared no competing interest.