[7] Yan N*, Li Y*, Xing Y, Wu J, Li J, Liang Y, Tang Y, Wang Z, Song H, Wang H, Xiao S, Lu M#. EMBO Rep 2022;23(6):e54147.

Abstract: Developmental arsenic exposure has been associated with cognitive deficits in epidemiological studies, but the underlying mechanisms remain poorly understood. Here, we establish a mouse model of developmental arsenic exposure exhibiting deficits of recognition and spatial memory in the offspring. These deficits are associated with genome-wide DNA hypomethylation and abnormal expression of cognition-related genes in the hippocampus. Arsenic atoms directly bind to the cysteine-rich ADD domain of DNA methyltransferase 3A (DNMT3A), triggering ubiquitin- and proteasome-mediated degradation of DNMT3A in different cellular contexts. DNMT3A degradation leads to genome-wide DNA hypomethylation in mouse embryonic fibroblasts but not in non-embryonic cell lines. Treatment with metformin, a first-line antidiabetic agent reported to increase DNA methylation, ameliorates the behavioral deficits and normalizes the aberrant expression of cognition-related genes and DNA methylation in the hippocampus of arsenic-exposed offspring. Our study establishes a DNA hypomethylation effect of developmental arsenic exposure and proposes a potential treatment against cognitive deficits in the offspring of pregnant women in arsenic-contaminated areas.
https://pubmed.ncbi.nlm.nih.gov/35373418/

[8] Lu M, Zak J, Chen S, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X#: A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway. Cell 2014, 157:1130-45.
https://pubmed.ncbi.nlm.nih.gov/24855949/
[9] Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler BM, Middleton MR, Siebold C, Jones EY, Sviderskaya EV, Cebon J, John T, Caballero OL, Goding CR, Lu X#: Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer Cell 2013, 23:618-33.
https://pubmed.ncbi.nlm.nih.gov/23623661/

[10] Lu M, Muers MR, Lu X#: Introducing STRaNDs: shuttling transcriptional regulators that are non-DNA binding. Nature Reviews Molecular Cell Biology 2016, 17:523-32.
https://pubmed.ncbi.nlm.nih.gov/27220640/