KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health DOI Open Access

Lindsey G Yoo,

D N Mendoza,

Allison J. Richard

и другие.

Genes, Год журнала: 2024, Номер 15(5), С. 639 - 639

Опубликована: Май 17, 2024

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents overview of emphasizing biological functions, which impact many cellular processes and range from chromatin remodeling genetic regulation. In model systems, KAT8’s acetylation H4 lysine 16 (H4K16) critical structure modification, influences gene expression, cell proliferation, differentiation, apoptosis. Furthermore, this summarizes the observed variability within KAT8 gene, underscoring implications various single nucleotide polymorphisms (SNPs) that affect functional efficacy are linked diverse phenotypic outcomes, ranging metabolic traits neurological disorders. Advanced insights into structural biology reveal interaction with multiprotein assemblies, such male-specific lethal (MSL) non-specific (NSL) complexes, regulate a wide transcriptional activities developmental functions. Additionally, focuses on roles homeostasis, stem identity, DNA damage repair, immune response, highlighting potential therapeutic target. The health disease, evidenced by recent studies, affirm importance physiology human pathology.

Язык: Английский

Processivity and specificity of histone acetylation by the male-specific lethal complex DOI Creative Commons

Anna E Kiss,

Anuroop Venkateswaran Venkatasubramani, Dilan Pathirana

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 52(9), С. 4889 - 4905

Опубликована: Фев. 26, 2024

Acetylation of lysine 16 histone H4 (H4K16ac) stands out among the modifications, because it decompacts chromatin fiber. The metazoan acetyltransferase MOF (KAT8) regulates transcription through H4K16 acetylation. Antibody-based studies had yielded inconclusive results about selectivity to acetylate N-terminus. We used targeted mass spectrometry examine activity in male-specific lethal core (4-MSL) complex on nucleosome array substrates. This is part Dosage Compensation Complex (DCC) that activates X-chromosomal genes male Drosophila. During short reaction times, acetylated efficiently and with excellent selectivity. Upon longer incubation, enzyme progressively lysines 12, 8 5, leading a mixture oligo-acetylated H4. Mathematical modeling suggests recognizes acetylates high selectivity, but remains substrate-bound continues more N-terminal processive manner. 4-MSL lacks non-coding roX RNA, critical component DCC. Remarkably, addition RNA non-specifically suppressed oligo-acetylation favor specific Because destabilizes MSL-nucleosome interaction vitro we speculate accelerates enzyme-substrate turn-over vivo, thus limiting processivity MOF, thereby increasing

Язык: Английский

Процитировано

1

KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health DOI Open Access

Lindsey G Yoo,

D N Mendoza,

Allison J. Richard

и другие.

Genes, Год журнала: 2024, Номер 15(5), С. 639 - 639

Опубликована: Май 17, 2024

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents overview of emphasizing biological functions, which impact many cellular processes and range from chromatin remodeling genetic regulation. In model systems, KAT8’s acetylation H4 lysine 16 (H4K16) critical structure modification, influences gene expression, cell proliferation, differentiation, apoptosis. Furthermore, this summarizes the observed variability within KAT8 gene, underscoring implications various single nucleotide polymorphisms (SNPs) that affect functional efficacy are linked diverse phenotypic outcomes, ranging metabolic traits neurological disorders. Advanced insights into structural biology reveal interaction with multiprotein assemblies, such male-specific lethal (MSL) non-specific (NSL) complexes, regulate a wide transcriptional activities developmental functions. Additionally, focuses on roles homeostasis, stem identity, DNA damage repair, immune response, highlighting potential therapeutic target. The health disease, evidenced by recent studies, affirm importance physiology human pathology.

Язык: Английский

Процитировано

1