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Journal ArticleDOI

The RNA Polymerase II Core Promoter – the Gateway to Transcription

01 Jun 2008-Current Opinion in Cell Biology (NIH Public Access)-Vol. 20, Iss: 3, pp 253-259
TL;DR: The core promoter is a sophisticated gateway to transcription that determines which signals will lead to transcription initiation and may contain many different sequence motifs that specify different mechanisms of transcription and responses to enhancers.
About: This article is published in Current Opinion in Cell Biology.The article was published on 2008-06-01 and is currently open access. It has received 380 citations till now. The article focuses on the topics: Transcription factor II D & RNA polymerase II.
Citations
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Journal ArticleDOI
TL;DR: Vertebrate CpG islands are generically equipped to influence local chromatin structure and simplify regulation of gene activity.
Abstract: Vertebrate CpG islands (CGIs) are short interspersed DNA sequences that deviate significantly from the average genomic pattern by being GC-rich, CpG-rich, and predominantly nonmethylated. Most, perhaps all, CGIs are sites of transcription initiation, including thousands that are remote from currently annotated promoters. Shared DNA sequence features adapt CGIs for promoter function by destabilizing nucleosomes and attracting proteins that create a transcriptionally permissive chromatin state. Silencing of CGI promoters is achieved through dense CpG methylation or polycomb recruitment, again using their distinctive DNA sequence composition. CGIs are therefore generically equipped to influence local chromatin structure and simplify regulation of gene activity.

2,710 citations


Cites background from "The RNA Polymerase II Core Promoter..."

  • ...Transcription factor binding at CGIs CGIs share little long-range sequence conservation, apart from an elevated CpG density and G+C content, and often lack core promoter elements such as the TATA box (Carninci et al. 2006; Juven-Gershon et al. 2008)....

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  • ...…GENES & DEVELOPMENT TATA boxes, along with other core promoter elements (such as the BRE, DPE, and DCE), tend to be associated with focused transcriptional initiation, whereas CGIs tend to lack these elements and display dispersed initiation patterns (for review, see Juven-Gershon et al. 2008)....

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Journal ArticleDOI
TL;DR: What high-resolution genome-wide maps of nucleosomes positions have taught us about how nucleosome positioning demarcates promoter regions and transcriptional start sites and how the composition and structure of promoter nucleosites facilitate or inhibit transcription is discussed.
Abstract: Knowing the precise locations of nucleosomes in a genome is key to understanding how genes are regulated. Recent 'next generation' ChIP-chip and ChIP-Seq technologies have accelerated our understanding of the basic principles of chromatin organization. Here we discuss what high-resolution genome-wide maps of nucleosome positions have taught us about how nucleosome positioning demarcates promoter regions and transcriptional start sites, and how the composition and structure of promoter nucleosomes facilitate or inhibit transcription. A detailed picture is starting to emerge of how diverse factors, including underlying DNA sequences and chromatin remodelling complexes, influence nucleosome positioning.

1,026 citations


Cites background from "The RNA Polymerase II Core Promoter..."

  • ...The conventional view is that most genes contain a predominant TSS, the location of which is defined by core promoter elements...

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Journal ArticleDOI
22 Feb 2013-Science
TL;DR: A precision nuclear run-on and sequencing assay to map the genome-wide distribution of transcriptionally engaged Pol II at base pair resolution and shows how the promoter dictates transcriptional pausing and detects the preferential localization of active transcription complexes within the genome.
Abstract: Transcription regulation occurs frequently through promoter-associated pausing of RNA polymerase II (Pol II) We developed a precision nuclear run-on and sequencing (PRO-seq) assay to map the genome-wide distribution of transcriptionally engaged Pol II at base pair resolution Pol II accumulates immediately downstream of promoters, at intron-exon junctions that are efficiently used for splicing, and over 3′ polyadenylation sites Focused analyses of promoters reveal that pausing is not fixed relative to initiation sites, nor is it specified directly by the position of a particular core promoter element or the first nucleosome Core promoter elements function beyond initiation, and when optimally positioned they act collectively to dictate the position and strength of pausing This "complex interaction" model was tested with insertional mutagenesis of the Drosophila Hsp70 core promoter

671 citations

Journal ArticleDOI
TL;DR: What is known about the mechanisms governing both global and gene-specific APA and the functional consequences of alternative polyadenylation are reviewed.

635 citations


Cites background from "The RNA Polymerase II Core Promoter..."

  • ...An interesting analogy is with TATA-less promoters, which use the same set of core transcription factors but involving different interactions with promoter sequences (Juven-Gershon et al., 2008; Sikorski and Buratowski, 2009)....

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Journal ArticleDOI
10 Sep 2009-Nature
TL;DR: These studies identify points in the transcription cycle where RNA polymerase II accumulates after encountering a rate-limiting step and identify key regulatory steps and factors and provide an understanding of the mechanistic generalities, as well as the rich diversities, of gene regulation.
Abstract: In the eukaryotic genome, the thousands of genes that encode messenger RNA are transcribed by a molecular machine called RNA polymerase II. Analysing the distribution and status of RNA polymerase II across a genome has provided crucial insights into the long-standing mysteries of transcription and its regulation. These studies identify points in the transcription cycle where RNA polymerase II accumulates after encountering a rate-limiting step. When coupled with genome-wide mapping of transcription factors, these approaches identify key regulatory steps and factors and, importantly, provide an understanding of the mechanistic generalities, as well as the rich diversities, of gene regulation.

575 citations


Cites background from "The RNA Polymerase II Core Promoter..."

  • ...In various combinations, the elements of the core promoter sequence target the assembly of distinct preinitiation complexes (PICs) composed of the general transcription factors (GTFs...

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References
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Journal ArticleDOI
18 May 2007-Cell
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.

6,488 citations

Journal ArticleDOI
01 May 1986-Nature
TL;DR: It is likely that most vertebrate genes are associated with ‘HTF islands’—DNA sequences in which CpG is abundant and non-methylated; however, highly tissue-specific genes, though, usually lack islands.
Abstract: It is likely that most vertebrate genes are associated with 'HTF islands'--DNA sequences in which CpG is abundant and non-methylated. Highly tissue-specific genes, though, usually lack islands. The contrast between islands and the remainder of the genome may identify sequences that are to be constantly available in the nucleus. DNA methylation appears to be involved in this function, rather than with activation of tissue specific genes.

3,673 citations

Journal ArticleDOI
TL;DR: Insight is given into the connections between chromatin modifications and transcriptional regulatory activity and a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2) is uncovered, providing a new tool for the functional annotation of the human genome.
Abstract: Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome.

3,215 citations

Journal ArticleDOI
13 Jul 2007-Cell
TL;DR: The results of a genome-wide analysis of human cells suggest that most protein-coding genes, including most genes thought to be transcriptionally inactive, experience transcription initiation, and that transcription initiation at most genes is a general phenomenon in human cells.

1,927 citations

Journal ArticleDOI
28 Jan 2005-Cell
TL;DR: Methylation patterns at orthologous loci are strongly conserved between human and mouse even though many methylated sites do not show sequence conservation notably higher than background, which suggests that the DNA elements that direct the methylation represent only a small fraction of the region or lie at some distance from the site.

1,536 citations

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