The establishment of active promoters in chromatin

Becker, Peter B.

doi:10.1002/bies.950160807

Cited by 72 publications

(45 citation statements)

References 62 publications

(42 reference statements)

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“…Several forms of ''dynamic competition'' (3,12,49) can account for the changes that occur at the enhancer. One type of mechanism supposes (i) that even when the Cyp1A1 gene is inactive, each chromatin subunit exists in equilibrium between a nucleosomal state (in which the DNA is ''inaccessible'') and a nonnucleosomal state (in which the DNA is ''accessible'') and (ii) that AhR/Arnt can only bind to DNA in the nonnucleosomal state.…”

Section: Discussionmentioning

confidence: 99%

Dioxin Induces Localized, Graded Changes in Chromatin Structure: Implications forCyp1A1Gene Transcription

Okino

Whitlock

1995

Molecular and Cellular Biology

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In mouse hepatoma cells, the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) induces Cyp1A1 gene transcription, a process that requires two basic helix-loop-helix regulatory proteins, the aromatic hydrocarbon receptor (AhR) and the aromatic hydrocarbon receptor nuclear translocator (Arnt). We have used a ligation-mediated PCR technique to analyze dioxin-induced changes in protein-DNA interactions and chromatin structure of the Cyp1A1 enhancer-promoter in its native chromosomal setting. Dioxin-induced binding of the AhR/Arnt heteromer to enhancer chromatin is associated with a localized (about 200 bp) alteration in chromatin structure that is manifested by increased accessibility of the DNA; these changes probably reflect direct disruption of a nucleosome by AhR/Arnt. Dioxin induces analogous AhR/Arnt-dependent changes in chromatin structure and accessibility at the Cyp1A1 promoter. However, the changes at the promoter must occur by a different, more indirect mechanism, because they are induced from a distance and do not reflect a local effect of AhR/Arnt binding. Dose-response experiments indicate that the changes in chromatin structure at the enhancer and promoter are graded and mirror the graded induction of Cyp1A1 transcription by dioxin. We discuss these results in terms of a TCDD-induced shift in an equilibrium between nucleosomal and nonnucleosomal chromatin configurations.

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Section: Discussionmentioning

confidence: 99%

Dioxin Induces Localized, Graded Changes in Chromatin Structure: Implications forCyp1A1Gene Transcription

Okino

Whitlock

1995

Molecular and Cellular Biology

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“…The ability of a transcription factor to bind to nucleosomes can be facilitated by the presence of multiple factor binding sites (84) (reviewed in Ref. 79). Thus, it is probably not fortuitous that p53 REs are composed of four half-sites and that p53 binds as a tetramer (85).…”

Section: Fig 6 P53 Interacts With P53 Res In Dna-damaged Hct116 Celmentioning

confidence: 99%

Constitutive DNase I Hypersensitivity of p53-Regulated Promoters

Braastad

Han

Hendrickson

2003

Journal of Biological Chemistry

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The ability of p53 to alter, at the transcriptional level, the gene expression of downstream targets is critical for its role as a tumor suppressor. Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators, histone acetyltransferases, and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction. We demonstrate here, however, that the promoter regions for the p53 target genes, p21, 14-3-3, and KARP-1, exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell. In contrast, p53 response elements, which resided outside the immediate promoter regions, existed within DNase I-resistant chromatin domains. Thus, p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element. As such, these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression.The differential chromatin structure and nuclease accessibility at a promoter region has long been recognized as a key distinguishing feature between active and inactive genes (reviewed in Ref. 1). Almost invariably, the promoter regions of active genes are marked experimentally by hypersensitivity to restriction endonucleases (2, 3) or, more commonly, DNase I (4). Although this hypersensitivity can be caused by torsional or topological stress in the DNA and distortions in the chromatin structure resulting from transcription factor binding, it is generally caused by the absence of nucleosomes or their remodeling (1, 4). The paucity of nucleosomes, in turn, is a direct consequence of the repressive effect that nucleosomes have on the transcriptional machinery and the requirement to alleviate that effect for productive transcription to occur (5-7). Thus, inactive genes usually have promoters that are nucleosomal, are insensitive to DNase I, and are regarded as being in a closed confirmation whereas active genes usually have core promoters that are nucleosome-free, hypersensitive to DNase I, and in an open configuration. Consequently, one of the hallmarks of gene induction mechanisms is the remodeling of the nucleosomal architecture of a promoter as it is activated (5, 6, 8).Enormous strides have been made in the last decade in understanding transcriptional activation at the chromatin level. In particular, the activation of expression of many, although not all (9 -11), inducible eukaryotic genes is consistent with what can collectively be called recruitment models of gene activation (3, 7, 8) (reviewed in Ref. 12). These models usually require, in response to some extracellular cue, the induction of a specific transcription factor and the subsequent interaction of that factor with its cognate response element, which is invariably a cis-acting ...

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“…There could be many factors contributing to the formation of each peak. For example, in addition to identification of the first HATs and HDACs, studies of chromatin structure per se and biochemical purification of ATP-dependent remodeling molecular machines were important for the surge of citation in the early and mid-1990s (for reviews, see Hansen and Ausio, 1992;Adams and Workman, 1993;Turner, 1993;Becker, 1994;Paranjape et al, 1994;Wolffe, 1994;Peterson and Tamkun, 1995 Figure 3 Schematic illustration of the prevalence of reversible lysine (K) acetylation in diverse cellular processes. The hexagon with the letter A refers to acetylation.…”

Section: Introductionmentioning

confidence: 99%