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Northwestern Medicine scientists have discovered how DNA methylation regulates spinal cord motor neurons. DNA methylation is an epigenetic mechanism that determines whether or not a gene is expressed, guides stem cells as they transform from blank slates into specialized cells, according to Evangelos Kiskinis, Ph.D., assistant professor of Neurology in the Division of Neuromuscular Disease and senior author of the study.
Motor neurons are special neuronal cells that link the central nervous system to muscle and degenerate in amyotrophic lateral sclerosis (ALS), called Lou Gehrig’s disease. After analyzing the stem cells, differentiating neural progenitors and the motor neuron populations, the enzyme DNMT3A triggered DNA methylation, which repressed counterintuitively activated the key transcription factors that controlled differentiation of stem cells into spinal cord motor neurons.
DNA methylation controls gene expression potential and cell identity, when stem cells transition from early progenitors to committed progenitors to developed neurons, DNA methylation allows suppression of key transcription factors. In turn, those transcription factors govern cell type function and specificity.
Epigenetics control different steps of the development of the human central nervous system by tuning the expression levels of transcription factors. Scientists discovered that irregular DNA methylation patterns could have downstream consequences related to the function of neurons, if DNA methylation patterns is not correct, there may be a cascade of irregular gene expression that causes the defective cells.
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