Neocortical RELN promoter methylation increases significantly after puberty

Reelin plays a pivotal role in neurodevelopment. Excessive RELN promoter methylation and/or decreased RELN gene expression have been described in schizophrenia and autism. We assessed RELN promoter methylation in post-mortem temporocortical tissue (Brodmann Area 41/42) of three prepuberal and six postpuberal normal individuals. The former display very little or no methylation, whereas most postpuberal individuals are heavily methylated, especially at CpG positions located between -131 and -98 bp (prepuberal vs. postpuberal, P<0.05). Sex hormones thus seemingly boost DNA methylation at the RELN promoter. This physiological change could significantly contribute to the onset of schizophrenia and the worsening of autistic behaviors, both typically occurring at puberty.