DNMT1 downregulation as well as its overexpression distinctly affect mostly overlapping genes implicated in schizophrenia, autism spectrum, epilepsy, and bipolar disorders.

ABSTRACT: Data on schizophrenia (SZ), epilepsy (EPD) and bipolar disorders (BPD) suggested an association of DNMT1 overexpression whereas certain variants of the gene were predicted to result in its increased expression in autism spectrum disorder (ASD). In addition, loss of DNMT1 in frontal cortex resulted in behavioral abnormalities in mice. Here we investigated the effects of increased as well as lack of DNMT1 expression using Dnmt1^tet/tet neurons as a model for abnormal neurogenesis and 10,861 genes showing transcript level dysregulation in datasets from the four disorders. In case of overexpression, 3,211 (∼ 30%) genes were dysregulated, affecting pathways involved in neurogenesis, semaphorin signaling, ephrin receptor activity, etc. A disproportionately higher proportion of d

SUBMITTER: Singh M 

PROVIDER: S-EPMC10731955 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature