Distinct Classes of Chromatin Loops Revealed by Deletion of an RNA-Binding Region in CTCF

Hansen, Anders S.; Hsieh, Tsung Han; Cattoglio, Claudia; Pustova, Iryna; Saldaña-Meyer, Ricardo; Reinberg, Danny; Darzacq, Xavier; Tjian, Robert

doi:10.1016/j.molcel.2019.07.039

Cited by 211 publications

(244 citation statements)

References 111 publications

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“…There is some controversy about which region of CTCF interacts with cohesin. While one report demonstrates physical interaction between the C terminal region of CTCF (amino acids 575 to 611) and the SA2 subunit of cohesin [37], other studies that deleted these amino acids (577-614) showed that they are dispensable [36, 55, 56]. In agreement with others, we find that RAD21 overlaps with CTCF binding and does not occupy sites bound exclusively by CTCFL ( Fig.…”

Section: Resultssupporting

confidence: 91%

“…Interestingly, clustering analysis of binding at CTCF and CTCFL only sites revealed that CLC is able to bind weakly to some CTCF only sites when CTCF is present but not when it is absent ( Figure S5D ), indicating that perhaps the N and C terminals of CTCF facilitate interaction between CTCF and CLC and this in turn directs binding of CLC to these sites. In support of this idea, recent studies have shown that an RNA binding region on the C terminal region of CTCF mediates CTCF clustering [56, 58]. Examples of fusion and parent protein binding are shown in the screenshots in Fig.…”

Section: Resultsmentioning

confidence: 77%

“…6d ). In this context it is pertinent to note that CTCF zinc fingers 1 and 10 have RNA binding regions that are important and may cooperate with the C terminal RNA binding region in oligomerization[55, 56].…”

Section: Resultsmentioning

confidence: 99%

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Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

Nishana

Rodriguez-Hernaez

et al. 2019

Preprint

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BackgroundUbiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL is normally only present in testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription.ResultsWe demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites, to regulate transcription, chromatin looping and insulation.ConclusionThis study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 77%

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Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

Nishana

Rodriguez-Hernaez

et al. 2019

Preprint

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“…Micro-C replaces the restriction enzyme used in Hi-C with micrococcal nuclease for digestion. Several groups recently used Micro-C to generate high-resolution contact maps of mouse and human cells highlighting its advantages over Hi-C and its potential to become an essential assay for nucleome studies [11,12]. The objective here was to assess the performance of Mustache on Micro-C data and evaluate the consistency of Micro-C loops when compared to Hi-C loops on the same cell line.…”

Section: Mustache Detects Loops That Are Consistent Between Hi-c and mentioning

confidence: 99%

“…To date, Hi-C has been the main assay of choice for discovering genome-wide chromatin contacts/interactions [8,9]. More recently, Micro-C [10], which replaces the restriction enzyme in Hi-C with micrococcal nuclease for digestion, enabled the generation nucleosome resolution chromosome folding maps of mouse and human cells [11,12]. With the decreasing cost of sequencing and optimization for smaller cell numbers, both Hi-C and Micro-C assays are expected to produce much higher resolution reference contact maps for a diverse set of organisms and cell lines [9,13,12].…”

Section: Introductionmentioning

confidence: 99%

Mustache: Multi-scale Detection of Chromatin Loops from Hi-C and Micro-C Maps using Scale-Space Representation

Ardakany

Gezer

Lonardi

et al. 2020

Preprint

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We present Mustache, a new method for multi-scale detection of chromatin loops from Hi-C and Micro-C contact maps. Mustache employs scale-space theory, a technical advance in computer vision, to detect blob-shaped objects in a multi-scale representation of chromatin contact maps parametrized by the size of the smoothing kernel. When applied to high-resolution Hi-C and Micro-C data, Mustache detects loops at a wide range of genomic distances, identifying potential structural and regulatory interactions that are supported by independent conformation capture experiments as well as by known correlates of loop formation such as CTCF binding, enhancers and promoters. Unlike the commonly used HiCCUPS tool, Mustache runs on general-purpose CPUs and it is very time efficient with a runtime of only a few minutes per chromosome for 5kb-resolution human genome contact maps. Extensive experimental results show that Mustache reports two to three times the number of HiCCUPS loops, which are reproducible across replicates. It also recovers a larger proportion of published ChIA-PET and HiChIP loops than HiCCUPS. A comparative analysis of Mustache's experimental results on Hi-C and Micro-C data confirms strong agreement between the two datasets with Micro-C providing better power for loop detection. Overall, our experimental results show that Mustache enables a more efficient and comprehensive analysis of the chromatin looping from high-resolution Hi-C and Micro-C datasets. Mustache is freely available at https://github.com/ay-lab/mustache.

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Expansion of the genotypic and phenotypic spectrum of CTCF‐related disorder guides clinical management: 43 new subjects and a comprehensive literature review

Morales

Wang

Garber

et al. 2022

American J of Med Genetics Pt A

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Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF‐related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient's diagnostic odyssey.

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Distinct Classes of Chromatin Loops Revealed by Deletion of an RNA-Binding Region in CTCF

Cited by 211 publications

References 111 publications

Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

Mustache: Multi-scale Detection of Chromatin Loops from Hi-C and Micro-C Maps using Scale-Space Representation

Expansion of the genotypic and phenotypic spectrum of CTCF‐related disorder guides clinical management: 43 new subjects and a comprehensive literature review

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