New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues

Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled...

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Autores principales:	John Wesley Pike, Mark B. Meyer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	vitamin D biology and action transcription ChIP-chip analysis distal enhancers histone H3 acetylation RNA polymerase II Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/810f5b77afbb494fa7ffe7e5a8e2bb31
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spelling	oai:doaj.org-article:810f5b77afbb494fa7ffe7e5a8e2bb312021-11-25T17:55:38ZNew Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues10.3390/ijms2222123521422-00671661-6596https://doaj.org/article/810f5b77afbb494fa7ffe7e5a8e2bb312021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12352https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled to next-generation DNA sequencing that have now been linked directly to CRISPR-Cas9 genomic editing in culture cells and in mouse tissues in vivo. Accordingly, these techniques have established that the vitamin D hormone modulates sets of cell-type specific genes via an initial action that involves rapid binding of the VDR–ligand complex to multiple enhancer elements at open chromatin sites that drive the expression of individual genes. Importantly, a sequential set of downstream events follows this initial binding that results in rapid histone acetylation at these sites, the recruitment of additional histone modifiers across the gene locus, and in many cases, the appearance of H3K36me3 and RNA polymerase II across gene bodies. The measured recruitment of these factors and/or activities and their presence at specific regions in the gene locus correlate with the emerging presence of cognate transcripts, thereby highlighting sequential molecular events that occur during activation of most genes both in vitro and in vivo. These features provide a novel approach to the study of vitamin D analogs and their actions in vivo and suggest that they can be used for synthetic compound evaluation and to select for novel tissue- and gene-specific features. This may be particularly useful for ligand activation of nuclear receptors given the targeting of these factors directly to genetic sites in the nucleus.John Wesley PikeMark B. MeyerMDPI AGarticlevitamin D biology and actiontranscriptionChIP-chip analysisdistal enhancershistone H3 acetylationRNA polymerase IIBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12352, p 12352 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vitamin D biology and action transcription ChIP-chip analysis distal enhancers histone H3 acetylation RNA polymerase II Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	vitamin D biology and action transcription ChIP-chip analysis distal enhancers histone H3 acetylation RNA polymerase II Biology (General) QH301-705.5 Chemistry QD1-999 John Wesley Pike Mark B. Meyer New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
description	Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled to next-generation DNA sequencing that have now been linked directly to CRISPR-Cas9 genomic editing in culture cells and in mouse tissues in vivo. Accordingly, these techniques have established that the vitamin D hormone modulates sets of cell-type specific genes via an initial action that involves rapid binding of the VDR–ligand complex to multiple enhancer elements at open chromatin sites that drive the expression of individual genes. Importantly, a sequential set of downstream events follows this initial binding that results in rapid histone acetylation at these sites, the recruitment of additional histone modifiers across the gene locus, and in many cases, the appearance of H3K36me3 and RNA polymerase II across gene bodies. The measured recruitment of these factors and/or activities and their presence at specific regions in the gene locus correlate with the emerging presence of cognate transcripts, thereby highlighting sequential molecular events that occur during activation of most genes both in vitro and in vivo. These features provide a novel approach to the study of vitamin D analogs and their actions in vivo and suggest that they can be used for synthetic compound evaluation and to select for novel tissue- and gene-specific features. This may be particularly useful for ligand activation of nuclear receptors given the targeting of these factors directly to genetic sites in the nucleus.
format	article
author	John Wesley Pike Mark B. Meyer
author_facet	John Wesley Pike Mark B. Meyer
author_sort	John Wesley Pike
title	New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
title_short	New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
title_full	New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
title_fullStr	New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
title_full_unstemmed	New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
title_sort	new approaches to assess mechanisms of action of selective vitamin d analogues
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/810f5b77afbb494fa7ffe7e5a8e2bb31
work_keys_str_mv	AT johnwesleypike newapproachestoassessmechanismsofactionofselectivevitamindanalogues AT markbmeyer newapproachestoassessmechanismsofactionofselectivevitamindanalogues
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New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues

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