Reprogramming of the epigenome in neurodevelopmental disorders

Area of Science:

• Neuroscience
• Genetics
• Epigenetics

Background:

• Neurodevelopmental disorders (NDDs) present complex etiological challenges.
• Many NDDs are linked to single-gene mutations affecting brain development.
• Chromatin regulation is frequently disrupted in NDDs, leading to overlapping symptoms like intellectual disability.

Purpose of the Study:

• To review epigenetic regulators mutated in NDDs.
• To highlight mutations in histone acetylation, methylation, and chromatin remodeling complexes.
• To explore the impact of histone germline mutations on neurological function.

Main Methods:

• Review of clinical sequencing studies and literature.
• Discussion of mechanistic investigations.
• Analysis of animal and induced pluripotent stem cell (iPSC) models.

Main Results:

• Epigenetic regulators (writers, erasers, readers, remodelers, histones) are implicated in NDDs.
• Mutations affect gene regulation at multiple levels of chromatin organization.
• Specific focus on histone acetylation, methylation, and chromatin remodeling complexes.

Conclusions:

• Understanding epigenetic mutations in NDDs is crucial for elucidating common pathogenic pathways.
• Classifying NDDs by their epigenetic impact can improve prognosis.
• This knowledge aids in understanding the role of epigenetic machinery in neurodevelopment and developing therapeutics.