Lysine Acetylation and Deacetylation in Brain Development and Neuropathies

Abstract

Embryonic development is critical for the final functionality and maintenance of the adult brain. Brain development is tightly regulated by intracellular and extracellular signaling. Lysine acetylation and deacetylation are posttranslational modifications that are able to link extracellular signals to intracellular responses. A wealth of evidence indicates that lysine acetylation and deacetylation are critical for brain development and functionality. Indeed, mutations of the enzymes and cofactors responsible for these processes are often associated with neurodevelopmental and psychiatric disorders. Lysine acetylation and deacetylation are involved in all levels of brain development, starting from neuroprogenitor survival and proliferation, cell fate decisions, neuronal maturation, migration, and synaptogenesis, as well as differentiation and maturation of astrocytes and oligodendrocytes, to the establishment of neuronal circuits. Hence, fluctuations in the balance between lysine acetylation and deacetylation contribute to the final shape and performance of the brain. In this review, we summarize the current basic knowledge on the specific roles of lysine acetyltransferase (KAT) and lysine deacetylase (KDAC) complexes in brain development and the different neurodevelopmental disorders that are associated with dysfunctional lysine (de)acetylation machineries.

Transcriptome-wide association study of attention deficit hyperactivity disorder identifies associated genes and phenotypes

“…The literature shows that ADHD has been associated with weaker function of the prefrontal cortex compared to healthy individuals 13 . KAT2B is a lysine histone acetyltranferase highly expressed in the brain 14 . Previous evidence has suggested that lysine acetylation is importance for brain function and proper development 14 .…”

“…KAT2B is a lysine histone acetyltranferase highly expressed in the brain 14 . Previous evidence has suggested that lysine acetylation is importance for brain function and proper development 14 . At another locus, TMEM161B, a transmembrane protein, had the highest posterior inclusion probability of 0.838 in the amygdala.…”

Identification of FMRP target genes expressed in corticogenesis: implication for common phenotypes among neurodevelopmental disorders

“…Among the four ASD-related FMRP targets we found, Kat6a and Kmt2c are previously suggested to be FMRP mRNA targets from ribosomal profiling using adult neurons (Darnell et al, 2011). Kat6a and Kmt2c are histone modification writers, which can epigenetically regulate transcription (Shen et al, 2014;Tapias and Wang, 2017).…”

Principal component analysis-based unsupervised feature extraction applied to single-cell gene expression analysis1

“…TAF7 was reported to play a critical role in embryonic development [32]. KAT2A, ATF2 and TAF1 were also suggested to be included in brain development [33]. BRCA1 has been shown to play critical roles in brain development [34].…”