scholarly journals In the loop: long range chromatin interactions and gene regulation

2011 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
A. Dean
Keyword(s):  
Gene Regulation ◽  
Long Range ◽  
Chromatin Interactions

scholarly journals CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

2020 ◽  
Author(s):  
Martin Franke ◽  
Elisa de la Calle-Mustienes ◽  
Ana Neto ◽  
Rafael Acemel ◽  
Juan Tena ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Long Range ◽  
Chromatin Structure ◽  
Ctcf Binding ◽  
Developmental Gene ◽  
Developmental Genes ◽  
Chromatin Interactions ◽  
Topologically Associating Domains ◽  
Regulatory Landscapes

Abstract CTCF is an 11-zinc-finger DNA-binding protein that acts as a transcriptional repressor and insulator as well as an architectural protein required for 3D genome folding. CTCF mediates long-range chromatin looping and is enriched at the boundaries of topologically associating domains, which are sub-megabase chromatin structures that are believed to facilitate enhancer-promoter interactions within regulatory landscapes. Although CTCF is essential for cycling cells and developing embryos, its in vitro removal has only modest effects over gene expression, challenging the concept that CTCF-mediated chromatin interactions and topologically associated domains are a fundamental requirement for gene regulation. Here we link the loss of chromatin structure and gene regulation in an in vivo model and during animal development. We generated a ctcf knockout mutant in zebrafish that allows us to monitor the effect of CTCF loss of function during embryo patterning and organogenesis. CTCF absence leads to loss of chromatin structure in zebrafish embryos and affects the expression of thousands of genes, including many developmental genes. In addition, chromatin accessibility, both at CTCF binding sites and cis-regulatory elements, is severely compromised in ctcf mutants. Probing chromatin interactions from developmental genes at high resolution, we further demonstrate that promoters fail to fully establish long-range contacts with their associated regulatory landscapes, leading to altered gene expression patterns and disruption of developmental programs. Our results demonstrate that CTCF and topologically associating domains are essential to regulate gene expression during embryonic development, providing the structural basis for the establishment of developmental gene regulatory landscapes.

scholarly journals CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

2020 ◽  
Author(s):  
Martin Franke ◽  
Elisa De la Calle-Mustienes ◽  
Ana Neto ◽  
Rafael D. Acemel ◽  
Juan J. Tena ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Long Range ◽  
Chromatin Structure ◽  
Ctcf Binding ◽  
Developmental Gene ◽  
Developmental Genes ◽  
Chromatin Interactions ◽  
Topologically Associating Domains ◽  
Regulatory Landscapes

CTCF is an 11-zinc-finger DNA-binding protein that acts as a transcriptional repressor and insulator as well as an architectural protein required for 3D genome folding1–5. CTCF mediates long-range chromatin looping and is enriched at the boundaries of topologically associating domains, which are sub-megabase chromatin structures that are believed to facilitate enhancer-promoter interactions within regulatory landscapes 6–12. Although CTCF is essential for cycling cells and developing embryos13,14, its in vitro removal has only modest effects over gene expression5,15, challenging the concept that CTCF-mediated chromatin interactions and topologically associated domains are a fundamental requirement for gene regulation16–18. Here we link the loss of chromatin structure and gene regulation in an in vivo model and during animal development. We generated a ctcf knockout mutant in zebrafish that allows us to monitor the effect of CTCF loss of function during embryo patterning and organogenesis. CTCF absence leads to loss of chromatin structure in zebrafish embryos and affects the expression of thousands of genes, including many developmental genes. In addition, chromatin accessibility, both at CTCF binding sites and cis-regulatory elements, is severely compromised in ctcf mutants. Probing chromatin interactions from developmental genes at high resolution, we further demonstrate that promoters fail to fully establish long-range contacts with their associated regulatory landscapes, leading to altered gene expression patterns and disruption of developmental programs. Our results demonstrate that CTCF and topologically associating domains are essential to regulate gene expression during embryonic development, providing the structural basis for the establishment of developmental gene regulatory landscapes.

scholarly journals Long-range chromatin interactions on the inactive X and at Hox clusters are regulated by the non-canonical SMC protein Smchd1

2018 ◽  
Author(s):  
Natasha Jansz ◽  
Andrew Keniry ◽  
Marie Trussart ◽  
Heidi Bildsoe ◽  
Tamara Beck ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Long Range ◽  
X Chromosome ◽  
Chromatin Structure ◽  
Short Range ◽  
Higher Order ◽  
Chromatin Interactions ◽  
Inactive X Chromosome ◽  
Hox Clusters

AbstractThe regulation of higher order chromatin structure is complex and dynamic; however we do not yet understand the full suite of mechanisms governing architecture. Here we reveal the non-canonical SMC protein Smchd1 as a novel regulator of long-range chromatin interactions, and add it to the canon of epigenetic proteins required for Hox gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes dependent on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we find increased short-range interactions and ectopic enhancer activation. By contrast, the inactive X chromosome is transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. There we observe spreading of H3K27me3 domains into regions not normally decorated by this mark. Together these data suggest Smchd1 has the capacity to insulate the chromatin, thereby limiting access to other chromatin modifying proteins.

scholarly journals CTCF, WAPL and PDS5 proteins control the formation of TADs and loops by cohesin

2017 ◽  
Author(s):  
Gordana Wutz ◽  
Csilla Várnai ◽  
Kota Nagasaka ◽  
David A Cisneros ◽  
Roman Stocsits ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Long Range ◽  
Direct Evidence ◽  
Chromatin Loops ◽  
Chromatin Interactions ◽  
Binding Partners ◽  
Topologically Associating Domains ◽  
Genome Wide ◽  
Mammalian Genomes

AbstractMammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.

scholarly journals HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

2021 ◽  
Vol 4 (3) ◽  
pp. 49
Author(s):  
Tomas Zelenka ◽  
Charalampos Spilianakis
Keyword(s):  
T Cells ◽  
Long Range ◽  
Three Dimensional ◽  
Cell Types ◽  
Range Interaction ◽  
Chromatin Interactions ◽  
Optimized Protocol ◽  
Long Range Interaction ◽  
Chromatin Compactness ◽  
Detailed Protocol

The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.

scholarly journals Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus

Cell Research ◽  
2014 ◽  
Vol 24 (5) ◽  
pp. 513-531 ◽  
Author(s):  
Jian-Feng Xiang ◽  
Qing-Fei Yin ◽  
Tian Chen ◽  
Yang Zhang ◽  
Xiao-Ou Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Long Range ◽  
Human Colorectal Cancer ◽  
Chromatin Interactions

scholarly journals Human PRE-PIK3C2B exhibits long-range intra- and inter-chromosomal interactions with genomic regions enriched in repressive marks

2020 ◽  
Author(s):  
Jayant Maini ◽  
Ankit Kumar Pathak ◽  
Kausik Bhattacharyya ◽  
Narendra Kumar ◽  
Ankita Narang ◽  
...  
Keyword(s):  
Long Range ◽  
Meta Analysis ◽  
Range Interaction ◽  
Dual Nature ◽  
Polycomb Response Element ◽  
Chromatin Interactions ◽  
Long Range Interaction ◽  
Intergenic Regions ◽  
Genomic Regions ◽  
Transcriptional Start Sites

AbstractHuman PRE-PIK3C2B is a dual nature polycomb response element that interacts with both polycomb as well as trithorax members. In the current study, using 4C-Seq (Capturing Circular Chromosomal Conformation-Sequencing), we identified long-range chromatin interactions associated with PRE-PIK3C2B and validated them with 3C-PCR. We identified both intra-as well as inter-chromosomal interactions, a large proportion of which were found to be closely distributed around transcriptional start sites (TSS). A significant number of interactions were also found to be associated with heterochromatic regions. Meta-analysis of ENCODE ChIP-Seq data identified an overall enrichment of YY1, CTCF as well as histone modification such as H3K4me3 and H3K27me marks in different cell lines. Almost 90% interactions were derived from either intronic or intergenic regions. among which large proportions of intronic interactors were either unique sequences or LINE/SINE derived. In case of intergenic interactions, majority of the interaction were associated with LINE/SINE repeats. We further found that genes proximal to the interactor sequences were co-expressed, they showed reduced expression. To the best of our knowledge this is one of the early demonstrations of long-range interaction of PRE sequences in human genome.

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