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The insulation of genes from external enhancers and silencing chromatin

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TLDR
DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes.
Abstract
Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5′ end of the chicken β-globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses both enhancer blocking activity and the ability to screen reporter genes against position effects. Enhancer blocking is associated with binding of the protein CTCF; sites that bind CTCF are found at other critical points in the genome. Protection against position effects involves other properties that appear to be associated with control of histone acetylation and methylation. Insulators thus are complex elements that can help to preserve the independent function of genes embedded in a genome in which they are surrounded by regulatory signals they must ignore.

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Citations
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Journal ArticleDOI

Looping and interaction between hypersensitive sites in the active β-globin locus

TL;DR: It is proposed that clustering of regulatory elements is key to creating and maintaining active chromatin domains and regulating transcription.
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Transcription regulation and animal diversity

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Transcriptional Regulatory Elements in the Human Genome

TL;DR: The methods currently used to identify transcriptional regulatory elements are discussed, and the ability of these methods to be scaled up for the purpose of annotating the entire human genome is discussed.
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Long-range control of gene expression: emerging mechanisms and disruption in disease.

TL;DR: Functional studies have shown many of these conserved sites to be transcriptional regulatory elements that sometimes reside inside unrelated neighboring genes, such sequence-conserved elements generally harbor sites for tissue-specific DNA-binding proteins.
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REGULATION OF TH2 DIFFERENTIATION AND Il4 LOCUS ACCESSIBILITY

TL;DR: The field is progressing toward an integrated model of the signaling and transcription factor networks, cis-regulatory elements, epigenetic modifications, and RNA interference mechanisms that converge to determine the lineage fate and gene expression patterns of differentiating helper T cells.
References
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Journal ArticleDOI

Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.

TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.

TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.
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Regulation of chromatin structure by site-specific histone H3 methyltransferases

TL;DR: A functional interdependence of site-specific H3 tail modifications is revealed and a dynamic mechanism for the regulation of higher-order chromatin is suggested.
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Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene

TL;DR: The results reveal that DNA methylation can control gene expression by modulating enhancer access to the gene promoter through regulation of an enhancer boundary.
Journal ArticleDOI

CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus

TL;DR: It is shown that CTCF, a zinc finger protein implicated in vertebrate boundary function, binds to several sites in the unmethylated imprinted-control region that are essential for enhancer blocking, the first example, to the authors' knowledge, of a regulated chromatin boundary in vertebrates.
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