Journal ArticleDOI
Long-range chromatin regulatory interactions in vivo
TLDR
The development of a widely applicable in situ technique to tag and recover chromatin in the immediate vicinity of an actively transcribed gene and provide the first direct evidence of long-range enhancer communication is reported.Abstract:
Communication between distal chromosomal elements is essential for control of many nuclear processes. For example, genes in higher eukaryotes often require distant enhancer sequences for high-level expression. The mechanisms proposed for long-range enhancer action fall into two basic categories. Non-contact models propose that enhancers act at a distance to create a favorable environment for gene transcription, or act as entry sites or nucleation points for factors that ultimately communicate with the gene. Contact models propose that communication occurs through direct interaction between the distant enhancer and the gene by various mechanisms that 'loop out' the intervening sequences. Although much attention has focused on contact models, the existence and nature of long-range interactions is still controversial and speculative, as there is no direct evidence that distant sequences physically interact in vivo. Here, we report the development of a widely applicable in situ technique to tag and recover chromatin in the immediate vicinity of an actively transcribed gene. We show that the classical enhancer element, HS2 of the prototypical locus control region (LCR) of the beta-globin gene cluster, is in close physical proximity to an actively transcribed HBB (beta-globin) gene located over 50 kb away in vivo, suggesting a direct regulatory interaction. The results give unprecedented insight into the in vivo structure of the LCR-gene interface and provide the first direct evidence of long-range enhancer communication.read more
Citations
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Journal ArticleDOI
An oestrogen-receptor-α-bound human chromatin interactome
Melissa J. Fullwood,Mei Hui Liu,You Fu Pan,Jun Liu,Han Xu,Yusoff Bin Mohamed,Yuriy L. Orlov,Stoyan Velkov,Andrea Ho,Poh Huay Mei,Elaine G.Y. Chew,Phillips Yao Hui Huang,Willem Welboren,Yuyuan Han,Hong Sain Ooi,Pramila N. Ariyaratne,Vinsensius B. Vega,Yanquan Luo,Peck Yean Tan,Pei Ye Choy,K. D. Senali Abayratna Wansa,Bing Zhao,Kar Sian Lim,Shi Chi Leow,Jit Sin Yow,Roy Joseph,Haixia Li,Kartiki V. Desai,Jane S. Thomsen,Yew Kok Lee,R. Krishna Murthy Karuturi,Thoreau Herve,Guillaume Bourque,Hendrik G. Stunnenberg,Xiaoan Ruan,Valere Cacheux-Rataboul,Wing-Kin Sung,Wing-Kin Sung,Edison T. Liu,Chia-Lin Wei,Edwin Cheung,Edwin Cheung,Edwin Cheung,Yijun Ruan,Yijun Ruan +44 more
TL;DR: It is proposed that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes and is described as a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global Chromatin interactions.
Journal ArticleDOI
Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers
Isaac B. Hilton,Anthony D'Ippolito,Christopher M. Vockley,Pratiksha I. Thakore,Gregory E. Crawford,Timothy E. Reddy,Charles A. Gersbach +6 more
TL;DR: A programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused to the catalytic core of the human acetyl transferase p300 is described, leading to robust transcriptional activation of target genes from promoters and both proximal and distal enhancers.
Journal ArticleDOI
Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements
Josée Dostie,Todd Richmond,Ramy Arnaout,Rebecca R. Selzer,William Lee,Tracey Honan,Eric D. Rubio,Anton Krumm,Justin Lamb,Chad Nusbaum,Roland Green,Job Dekker +11 more
TL;DR: A high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods that should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure.
Journal ArticleDOI
Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions.
TL;DR: ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous, and generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.
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.
References
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Journal ArticleDOI
Going the distance: a current view of enhancer action.
TL;DR: Current models regarding the role of enhancers in the regulation of transcription by RNA polymerase II are presented.
Journal ArticleDOI
The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants
TL;DR: The possibility that the 72 bp repeat region in SV40 may act as a bi-directional entry site for RNA polymerase B such that promoter sequences linked to the repeat are more efficiently utilised is discussed.
Journal ArticleDOI
Transcription complex stability and chromatin dynamics in vivo
TL;DR: Visualization of transcriptional activity of genes that compete for distant elements, using the globin locus as a model, has revealed the dynamics of chromatin interactions in vivo.
Journal ArticleDOI
Active RNA polymerases are localized within discrete transcription "factories' in human nuclei.
TL;DR: Results are consistent with transcription occurring as templates slide past attached polymerases, as nascent RNA is extruded into the factories, which the authors call transcription 'factories'.
Journal ArticleDOI
Looping versus linking: toward a model for long-distance gene activation
Michael Bulger,Mark Groudine +1 more
TL;DR: Models for the establishment of active chromatin domains by LCRs are summarized and the evidence for the looping model of long-distance gene activation of enhancer and LCR function is described.