Abstract
Using a "crude" chromatin-based transcription system that mimics transactivation by RAR/RXR heterodimers in vivo, we could not demonstrate that chromatin remodeling was required to relieve nucleosomal repression. Using "purified" chromatin templates, we show here that, irrespective of the presence of histone H1, both ATP-driven chromatin remodeling activities and histone acetyltransferase (HAT) activities of coactivators recruited by liganded receptors are required to achieve transactivation. DNA footprinting, ChIP analysis, and order of addition experiments indicate that coactivator HAT activities and two ATP-driven remodeling activities are sequentially involved at distinct steps preceding initiation of transcription. Thus, both ATP-driven chromatin remodeling and HAT activities act in a temporally ordered and interdependent manner to alleviate the repressive effects of nucleosomal histones on transcription by RARalpha/RXRalpha heterodimers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyl Coenzyme A / metabolism
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Acetylation / drug effects
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Acetyltransferases / metabolism*
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Adenosine Triphosphate / metabolism*
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Animals
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Cattle
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Chromatin / chemistry*
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Chromatin / drug effects
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Chromatin / genetics
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Chromatin / metabolism*
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DNA Helicases
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DNA-Binding Proteins / metabolism
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Dimerization
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Histone Acetyltransferases
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Histones / chemistry
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Histones / metabolism
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Humans
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Ligands
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Macromolecular Substances
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Molecular Conformation
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Nuclear Proteins / metabolism
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Nuclear Receptor Coactivator 2
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Promoter Regions, Genetic / genetics
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Protein Binding
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Receptors, Retinoic Acid / metabolism*
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Response Elements / genetics
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Retinoid X Receptors
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Retinoids / pharmacology
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Saccharomyces cerevisiae Proteins*
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Templates, Genetic
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Time Factors
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
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Transcriptional Activation* / drug effects
Substances
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Chromatin
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DNA-Binding Proteins
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Histones
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Ligands
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Macromolecular Substances
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Nuclear Proteins
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Nuclear Receptor Coactivator 2
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Receptors, Retinoic Acid
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Retinoid X Receptors
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Retinoids
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SMARCA1 protein, human
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SMARCA2 protein, human
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SNF2L protein, Bos taurus
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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Acetyl Coenzyme A
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Adenosine Triphosphate
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Acetyltransferases
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Histone Acetyltransferases
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SMARCA4 protein, human
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DNA Helicases