Brian R Keppler1, Trevor K Archer. 1. National Institutes of Health, National Institute of Environmental Health Sciences, North Carolina 27709, USA. archer1@niehs.nih.gov
Abstract
BACKGROUND: Part 1 of this review described the importance of histone acetylases, deacetylases, methylases and demethylases in transcriptional control and their potential as therapeutic targets. However, precise gene regulation requires the involvement of more than just the addition or removal of acetyl and methyl groups on histones. Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity. Accordingly, the enzymes responsible for these modifications are also misregulated in various disease states. OBJECTIVE: To review the complex roles of chromatin-modifying enzymes in gene regulation and to highlight their potential as therapeutic targets. METHODS: This review is based on recent published literature and online resources. RESULTS/ CONCLUSION: In this second and final part of the review, we discuss the importance of these other histone and nucleosome modifying enzymes in gene transcription as well as their therapeutic potential.
BACKGROUND: Part 1 of this review described the importance of histone acetylases, deacetylases, methylases and demethylases in transcriptional control and their potential as therapeutic targets. However, precise gene regulation requires the involvement of more than just the addition or removal of acetyl and methyl groups on histones. Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity. Accordingly, the enzymes responsible for these modifications are also misregulated in various disease states. OBJECTIVE: To review the complex roles of chromatin-modifying enzymes in gene regulation and to highlight their potential as therapeutic targets. METHODS: This review is based on recent published literature and online resources. RESULTS/ CONCLUSION: In this second and final part of the review, we discuss the importance of these other histone and nucleosome modifying enzymes in gene transcription as well as their therapeutic potential.
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