The impact of genetic mutations in epigenetic factors on brain development and neurodevelopmental disorders

Brain development is tightly controlled at many different levels that work in harmony to ensure the proper structure and function of brain cells. Such regulatory processes act at the level of genomic DNA (deoxyribonucleic acid) composition and fundamental cellular events that control gene transcription, transcript processing/alternative splicing, and protein translation. Both genetics and epigenetics control the gene expression program of every single cell, the latter referring to the regulatory processes that are not reflected in the order of DNA sequences. Epigenetic regulation mainly includes modification of DNA molecules (DNA methylation) or chemical changes in amino acid residues of DNA-bound proteins (histone posttranslational modifications). The combination of DNA and histone proteins constitutes the chromatin. The crosstalk between DNA and histone proteins and their different epigenetic modifications affects chromatin organization, resulting in active and inactive chromatin compartments. Importantly, genetic mutation of epigenetic factors may impact the process of brain development and function throughout life. In this chapter, we will focus on epigenetic factors that are involved in DNA methylation and histone modifications, known as "writers, readers, and erasers/modifiers." A brief section is also included on regulatory RNA (ribonucleic acid) molecules that may impact gene expression. Lastly, we will provide some context on the impact of genetic mutations on epigenetic factors that may lead to neurodevelopmental disorders.