Epigenomic Programming in Early Fetal Brain Development

Abstract

Aim: To provide a comprehensive understanding of gene regulatory networks in the developing human brain and a foundation for interpreting pathogenic deregulation. Materials & methods: We generated reference epigenomes and transcriptomes of dissected brain regions and primary neural progenitor cells (NPCs) derived from cortical and ganglionic eminence tissues of four normal human fetuses. Results: Integration of these data across developmental stages revealed a directional increase in active regulatory states, transcription factor activities and gene transcription with developmental stage. Consistent with differences in their biology, NPCs derived from cortical and ganglionic eminence regions contained common, region specific, and gestational week specific regulatory states. Conclusion: We provide a high-resolution regulatory network for NPCs from different brain regions as a comprehensive reference for future studies.

Fetal origin of sex‐bias brain aging

“…DNA methylation changes in the brain throughout life 22,79,80 . Our data revealed the patterns how methylation changes occur in the brain as mice age.…”

Fetal origin of sex-bias brain aging

“…DNA methylation changes in the brain throughout life (18, 79, 80). Our data showed that there are patterns how these changes in brain as mice age.…”

Implications of Extended Inhibitory Neuron Development

“…In mammals, the DNA methylation status of the maternal oxytocin gene promoter during the mid-late gestation of human pregnancy is associated with specific maternal behaviors, such as intrusiveness [ 44 ]. Recent epigenetic neurodevelopmental studies in the mouse brain identified that chromatin methylation in neuronal progenitor cells can regulate neurogenesis [ 45 , 46 ]. DNA methylation is catalyzed by an enzymatic family of DNA methyltransferases (DNMTs; DNMT1 and DNMT3).…”

“…Additionally, human fetal brains in the first and second trimesters also display significant changes in DNA methylation of the promoter regulatory regions of the genes involved in neurodevelopmental processes, such as MEIS1 (homeobox gene), NF1C (nuclear factor 1 C-type), and FAM49A (carrying cytoplasmic fragile X-interacting superfamily sequences) [ 46 ]. Given that human fetal-specific epigenetic machinery and methylation modifications are identified in the proliferative zones of both the cortical and GE regions [ 45 , 55 ], inhibitory neurogenesis in the human fetal brain is likely to be influenced by epigenomic plasticity. However, little is known about how epigenetic mechanisms specifically regulate the GABAergic inhibitory neurogenesis for more protracted periods and what their differences are across species.…”