Impaired Regulation of Histone Methylation and Acetylation Underlies Specific Neurodevelopmental Disorders

Frontiers in Genetics

Merrick S. Fallah¹  Dora Szarics¹  Clara M. Robson¹  James H. Eubanks² 

[1] Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;Department of Physiology, University of Toronto, Toronto, ON, Canada;Department of Surgery (Neurosurgery), University of Toronto, Toronto, ON, Canada;Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;

关键词: epigenetics;    histone;    acetylation;    methylation;    neurodevelopment;   

DOI  :  10.3389/fgene.2020.613098

来源: DOAJ

【 摘 要 】

Epigenetic processes are critical for governing the complex spatiotemporal patterns of gene expression in neurodevelopment. One such mechanism is the dynamic network of post-translational histone modifications that facilitate recruitment of transcription factors or even directly alter chromatin structure to modulate gene expression. This is a tightly regulated system, and mutations affecting the function of a single histone-modifying enzyme can shift the normal epigenetic balance and cause detrimental developmental consequences. In this review, we will examine select neurodevelopmental conditions that arise from mutations in genes encoding enzymes that regulate histone methylation and acetylation. The methylation-related conditions discussed include Wiedemann-Steiner, Kabuki, and Sotos syndromes, and the acetylation-related conditions include Rubinstein-Taybi, KAT6A, genitopatellar/Say-Barber-Biesecker-Young-Simpson, and brachydactyly mental retardation syndromes. In particular, we will discuss the clinical/phenotypic and genetic basis of these conditions and the model systems that have been developed to better elucidate cellular and systemic pathological mechanisms.

【 授权许可】

Unknown