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

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 t...

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Main Authors: Chenise O’Garro, Loveth Igbineweka, Zonaira Ali, Mihaly Mezei, Shiraz Mujtaba
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/3/455
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author Chenise O’Garro
Loveth Igbineweka
Zonaira Ali
Mihaly Mezei
Shiraz Mujtaba
author_facet Chenise O’Garro
Loveth Igbineweka
Zonaira Ali
Mihaly Mezei
Shiraz Mujtaba
author_sort Chenise O’Garro
collection DOAJ
description 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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spelling doaj.art-862029ea445c40cdbbf14a3838a979722023-11-21T11:02:48ZengMDPI AGBiomolecules2218-273X2021-03-0111345510.3390/biom11030455The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential TherapeuticsChenise O’Garro0Loveth Igbineweka1Zonaira Ali2Mihaly Mezei3Shiraz Mujtaba4Department of Biology, Medgar Evers College, City University of New York, Brooklyn, NY 11225, USADepartment of Biology, Medgar Evers College, City University of New York, Brooklyn, NY 11225, USADepartment of Biology, Medgar Evers College, City University of New York, Brooklyn, NY 11225, USADepartment of Pharmaceutical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Biology, Medgar Evers College, City University of New York, Brooklyn, NY 11225, USAThe 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.https://www.mdpi.com/2218-273X/11/3/455epigenetic modificationsacetylationlysine acetyltransferasesgene regulationmolecular interactions and biological outcomes
spellingShingle Chenise O’Garro
Loveth Igbineweka
Zonaira Ali
Mihaly Mezei
Shiraz Mujtaba
The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
Biomolecules
epigenetic modifications
acetylation
lysine acetyltransferases
gene regulation
molecular interactions and biological outcomes
title The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
title_full The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
title_fullStr The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
title_full_unstemmed The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
title_short The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics
title_sort biological significance of targeting acetylation mediated gene regulation for designing new mechanistic tools and potential therapeutics
topic epigenetic modifications
acetylation
lysine acetyltransferases
gene regulation
molecular interactions and biological outcomes
url https://www.mdpi.com/2218-273X/11/3/455
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