Nicole Hamagami-Samson
Program: Molecular Genetics and Genomics
Current advisor: Harrison W. Gabel, PhD
Undergraduate university: Bryn Mawr College
Research summary
I defended my dissertation in April 2024 in the lab of Dr. Harrison Gabel, which primarily studies unique molecular mechanisms of transcriptional regulation in the mammalian brain. The lab has previously found that MeCP2 binds to non-CpG DNA methylation and regulates long neuronal genes in the brain. Specifically, we have found that MeCP2 represses enhancers within long neuronal genes containing high non-CG methylation and that disruption of MeCP2 can lead to aberrant enhancer activation and subsequent neuronal gene dysfunction. My PhD project involved characterizing various histone marks and transcriptional regulators upstream of MeCP2 to elucidate how non-CG methylation is established across the neuronal genome. The findings of this analysis can help us better understand the molecular etiology of neurodevelopmental disorders, such as Rett syndrome and MeCP2 duplication syndrome, caused by disruption of epigenetic regulation in neurons.
Graduate publications
Hamagami N, Wu DY, Clemens AW, Nettles SA, Li A, Gabel HW. 2023 NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons. Mol Cell, 83(9):1412-1428.e7.
Beard DC, Zhang X, Wu DY, Martin JR, Erickson A, Boua JV, Hamagami N, Swift RG, McCullough KB, Ge X, Bell-Hensley A, Zheng H, Palmer CW, Fuhler NA, Lawrence AB, Hill CA, Papouin T, Noguchi KK, McAlinden A, Garbow JR, Dougherty JD, Maloney SE, Gabel HW. 2023 Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits. Cell Rep, 42(11):113411.