Insulators: exploiting transcriptional and epigenetic mechanisms
Miklos Gaszner,Gary Felsenfeld +1 more
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TLDR
New insights suggest that the mechanisms of action of both enhancer blockers and barriers might not be unique to these types of element, but instead are adaptations of other gene-regulatory mechanisms.Abstract:
Insulators are DNA sequence elements that prevent inappropriate interactions between adjacent chromatin domains. One type of insulator establishes domains that separate enhancers and promoters to block their interaction, whereas a second type creates a barrier against the spread of heterochromatin. Recent studies have provided important advances in our understanding of the modes of action of both types of insulator. These new insights also suggest that the mechanisms of action of both enhancer blockers and barriers might not be unique to these types of element, but instead are adaptations of other gene-regulatory mechanisms.read more
Citations
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High-resolution profiling of histone methylations in the human genome.
Artem Barski,Suresh Cuddapah,Kairong Cui,Tae-Young Roh,Dustin E. Schones,Zhibin Wang,Gang Wei,Iouri Chepelev,Keji Zhao +8 more
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.
Journal ArticleDOI
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Suhas S.P. Rao,Miriam H. Huntley,Neva C. Durand,Elena K. Stamenova,Ivan D. Bochkov,James T. Robinson,James T. Robinson,Adrian L. Sanborn,Ido Machol,Ido Machol,Arina D. Omer,Arina D. Omer,Eric S. Lander,Eric S. Lander,Eric S. Lander,Erez Lieberman Aiden +15 more
TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.
Journal ArticleDOI
The accessible chromatin landscape of the human genome
Robert E. Thurman,Eric Rynes,Richard Humbert,Jeff Vierstra,Matthew T. Maurano,Eric Haugen,Nathan C. Sheffield,Andrew B. Stergachis,Hao Wang,Benjamin Vernot,Kavita Garg,Sam John,Richard Sandstrom,Daniel Bates,Lisa Boatman,Theresa K. Canfield,Morgan Diegel,Douglas Dunn,Abigail K. Ebersol,Tristan Frum,Erika Giste,Audra K. Johnson,Ericka M. Johnson,Tanya Kutyavin,Bryan R. Lajoie,Bum Kyu Lee,Kristen Lee,Darin London,Dimitra Lotakis,Shane Neph,Fidencio Neri,Eric D. Nguyen,Hongzhu Qu,Hongzhu Qu,Alex Reynolds,Vaughn Roach,Alexias Safi,Minerva E. Sanchez,Amartya Sanyal,Anthony Shafer,Jeremy M. Simon,Lingyun Song,Shinny Vong,Molly Weaver,Yongqi Yan,Zhancheng Zhang,Zhuzhu Zhang,Boris Lenhard,Muneesh Tewari,Michael O. Dorschner,R. Scott Hansen,Patrick A. Navas,George Stamatoyannopoulos,Vishwanath R. Iyer,Jason D. Lieb,Shamil R. Sunyaev,Joshua M. Akey,Peter J. Sabo,Rajinder Kaul,Terrence S. Furey,Job Dekker,Gregory E. Crawford,John A. Stamatoyannopoulos,John A. Stamatoyannopoulos +63 more
TL;DR: The first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types is presented, revealing novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.
Journal ArticleDOI
Transposable elements and the epigenetic regulation of the genome.
TL;DR: New insights have been gained into how silencing in eukaryotic cells has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome.
Journal ArticleDOI
Transcription factors: from enhancer binding to developmental control.
TL;DR: Current knowledge of transcription factor function from genomic and genetic studies is reviewed and how different strategies, including extensive cooperative regulation, progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development are discussed.
References
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Journal ArticleDOI
Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.
Tom Volpe,Catherine A. Kidner,Ira M. Hall,Ira M. Hall,Grace Teng,Grace Teng,Shiv I. S. Grewal,Robert A. Martienssen +7 more
TL;DR: It is proposed that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.
Journal ArticleDOI
Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene
Adam C. Bell,Gary Felsenfeld +1 more
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
Amy T. Hark,Christopher J. Schoenherr,David J. Katz,Robert S. Ingram,John Levorse,Shirley M. Tilghman +5 more
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.
Journal ArticleDOI
The Protein CTCF Is Required for the Enhancer Blocking Activity of Vertebrate Insulators
TL;DR: A 42 bp fragment of the chicken beta-globin insulator is identified that is both necessary and sufficient for enhancer blocking activity in human cells and suggests that directional enhancerblocking by CTCF is a conserved component of gene regulation in vertebrates.
Journal ArticleDOI
Active genes dynamically colocalize to shared sites of ongoing transcription.
Cameron S. Osborne,Lyubomira Chakalova,Karen E. Brown,David R. F. Carter,David R. F. Carter,Alice Horton,Emmanuel Debrand,Beatriz Goyenechea,Jennifer A. Mitchell,Susana Lopes,Susana Lopes,Wolf Reik,Peter Fraser +12 more
TL;DR: It is shown that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies.