The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology

Wiesel-Motiuk, Naama; Assaraf, Yehuda G.

doi:10.1016/j.drup.2020.100729

Cited by 45 publications

(47 citation statements)

References 176 publications

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“…heterozygous mice also displayed a decrease in the number of PV + interneurons [30,53]. Moz and Morf (two of the three enzymes Brpf1 binds) were involved in regulating neurogenesis [54][55][56]. Morf mutant mice showed reduced ability of neural stem cells/progenitor cells differentiating into neurons, astrocytes, and oligodendrocytes, but not limited to specific neuronal types [54].…”

Section: Discussionmentioning

confidence: 99%

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Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

You

Cao

Xian

et al. 2021

Preprint

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Intellectual disability is closely related to impaired GABA neurotransmission. Brpf1 was specifically expressed in medial ganglionic eminence (MGE), a developmental niche of GABAergic interneurons, and patients with BRPF1 mutations were mentally retarded. To test its role in development and function of MGE-derived GABAergic interneurons, we performed immunofluorescence staining, whole-cell patch-clamp, MGE transplantation and mRNA-Seq to understand its effect on neuronal differentiation, dendritic morphology, electrophysiology, migration and gene regulation, using mouse MGE-derived GABAergic interneurons infected with AAV-shBrpf1. We found a decreasing trend on parvalbumin+ interneuron differentiation. Moreover, increased firing threshold, decreased number of evoked APs, and a reduced amplitude of mIPSCs were observed before any significant change of MAP2+ dendritic morphology and in vivo migration appeared. Finally, mRNA-Seq analysis revealed that genes related to neurodevelopment and synaptic transmission such as Map2k7 were dysregulated. Our results demonstrated a key role of Brpf1 in inhibitory neurotransmission and related gene expression of GABAergic interneurons.

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Section: Discussionmentioning

confidence: 99%

“…Dysregulation of excitatory/inhibitory neuronal circuits was closely related to various neurodevelopmental disorders [57][58][59] phosphorylation [56], and patients with JNK mutations were detected with ID [61].…”

Section: Discussionmentioning

confidence: 99%

Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

You

Cao

Xian

et al. 2021

Preprint

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“…Missense, inactivating, and truncation mutations within KAT3A/-3B may cause breast, gastric, ovarian, and small-cell lung cancers as well as diffuse, large cell, and follicular lymphoma [ 72 ]. Deletion, amplification, and translocation of the KAT6B gene can lead to leiomyoma and bladder, colorectal, and small-cell lung cancers [ 176 ]. Together, these data suggest that the functions of KATs have been characterized better in disease situations than in normal cells.…”

Section: Acetylation Of Nonhistone Proteinsmentioning

confidence: 99%

“…The MYST family of KATs (which includes KAT5, -6A, -6B, -7, and -8) plays a central role in maintaining cellular homeostasis and stem cell patterning during embryogenesis [ 102 , 129 , 176 ]. These KATs are also involved in regulating DNA damage responses, cell cycle control, and apoptotic pathways [ 47 ].…”

Section: Acetylation Of Nonhistone Proteinsmentioning

confidence: 99%

“…A KAT6A-TIF2 fusion protein suppresses the expression of CDKN2A , which leads to the downregulation of cellular senescence [ 93 ]. The human KAT6A gene was first identified in patients with acute myeloid leukemia [ 176 ]. The KAT6A and -6B genes are composed of plant homeodomain, serine-rich, and methionine-rich domains.…”

Section: Acetylation Of Nonhistone Proteinsmentioning

confidence: 99%

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The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics

et al. 2021

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The molecular interplay between nucleosomal packaging and the chromatin landscape regulates the transcriptional programming and biological outcomes of downstream genes. An array of epigenetic modifications plays a pivotal role in shaping the chromatin architecture, which controls DNA access to the transcriptional machinery. Acetylation of the amino acid lysine is a widespread epigenetic modification that serves as a marker for gene activation, which intertwines the maintenance of cellular homeostasis and the regulation of signaling during stress. The biochemical horizon of acetylation ranges from orchestrating the stability and cellular localization of proteins that engage in the cell cycle to DNA repair and metabolism. Furthermore, lysine acetyltransferases (KATs) modulate the functions of transcription factors that govern cellular response to microbial infections, genotoxic stress, and inflammation. Due to their central role in many biological processes, mutations in KATs cause developmental and intellectual challenges and metabolic disorders. Despite the availability of tools for detecting acetylation, the mechanistic knowledge of acetylation-mediated cellular processes remains limited. This review aims to integrate molecular and structural bases of KAT functions, which would help design highly selective tools for understanding the biology of KATs toward developing new disease treatments.

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Epigenetic regulation of craniofacial development and disease

Shull,

Artinger

2023

Birth Defects Research

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BackgroundThe formation of the craniofacial complex relies on proper neural crest development. The gene regulatory networks (GRNs) and signaling pathways orchestrating this process have been extensively studied. These GRNs and signaling cascades are tightly regulated as alterations to any stage of neural crest development can lead to common congenital birth defects, including multiple syndromes affecting facial morphology as well as nonsyndromic facial defects, such as cleft lip with or without cleft palate. Epigenetic factors add a hierarchy to the regulation of transcriptional networks and influence the spatiotemporal activation or repression of specific gene regulatory cascades; however less is known about their exact mechanisms in controlling precise gene regulation.AimsIn this review, we discuss the role of epigenetic factors during neural crest development, specifically during craniofacial development and how compromised activities of these regulators contribute to congenital defects that affect the craniofacial complex.

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The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology

Cited by 45 publications

References 176 publications

Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics

Epigenetic regulation of craniofacial development and disease

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