Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding

Hsieh, Tsung Han; Cattoglio, Claudia; Slobodyanyuk, Elena; Hansen, Anders S.; Rando, Oliver J.; Tjian, Robert; Darzacq, Xavier

doi:10.1016/j.molcel.2020.03.002

Cited by 499 publications

(594 citation statements)

References 94 publications

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“…We ran MUSTACHE on (i) Hi-C contact maps for human cell lines GM12878 and K562 obtained from Rao et al [9], (ii) Hi-C and Micro-C contact maps of HFFc6 cell line obtained from Krietenstein et al [12], and (iii) Micro-C contact maps of mouse embryonic stem cell (mESC) from Hsieh et al [25] (Additional file 1: Table S1). For assessing the consistency of loop calls at different resolutions and for measuring reproducibility across replicates, we also used 10 kb GM12878 Hi-C contact maps.…”

Section: Mustache Detects Chromatin Loops From Publicly Available Conmentioning

confidence: 99%

Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

et al. 2020

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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 contact maps. Mustache is scalable to kilobase-resolution maps and reports loops that are highly consistent between replicates and between Hi-C and Micro-C datasets. Compared to other loop callers, such as HiCCUPS and SIP, Mustache recovers a higher number of published ChIA-PET and HiChIP loops as well as loops linking promoters to regulatory elements. Overall, Mustache enables an efficient and comprehensive analysis of chromatin loops. Available at: https://github.com/ay-lab/mustache.

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Section: Mustache Detects Chromatin Loops From Publicly Available Conmentioning

confidence: 99%

Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

et al. 2020

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“…Down-modulation of CTCF/CBE activity allows RC-bound RAG to scan various linear distances across the Igh in some cases the full-length. Upon reaching remaining scanning impediments, which could reflect transcription (dark arrows) 11,37,46 , transcription-factor (TF)-binding sites 15,[21][22][23]38,39 (orange diamonds), and/or CBEs with residual CTCF binding, impeded scanning focuses RC-based RAG activity on sequences in the impeded region 11 for VH-to-DJH joining 1 (e). Down-modulation of CTCF binding activity is one manner for extending extrusion but this could also be achieved by circumventing CBE impediments, for example, through modulation of cohesin activity (See Text).…”

Section: Gromentioning

confidence: 99%

CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning

Lou

Dring

et al. 2020

Preprint

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RAG endonuclease initiates V(D)J recombination in progenitor (pro)-B cells 1 . Upon binding a recombination center (RC)-based JH, RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin 2-10 , to locate Ds and assemble a DJH-based RC 11 . CTCF looping factor-bound elements (CBEs) within IGCR1 upstream of Ds impede RAG-scanning 12-15 ; but their inactivation allows scanning to proximal VHs where additional CBEs activate rearrangement and impede scanning any further upstream 15,16 . Distal VH utilization is thought to involve diffusional RC access following large-scale Igh locus contraction 17-23 . Here, we test the potential of linear RAG-scanning to mediate distal VH usage in G1-arrested, v-Abl-pro-B cell lines 24,25 , which undergo robust D-to-JH but little VH-to-DJH rearrangements, presumably due to lack of locus contraction 11,15 . Through an auxin-inducible approach 26,27 , we degrade the cohesin-component Rad21 4,7,27 or CTCF 7,9 in these G1-arrested lines, which maintain substantial viability throughout four-day experiments. Rad21 degradation eliminated all V(D)J recombination and RAG-scanning-associated interactions, except RC-located DQ52-to-JH joining in which synapsis occurs by diffusion 11 . Remarkably, while CTCF degradation suppressed most CBE-based chromatin interactions, it promoted robust RC interactions with, and robust VH-to-DJH joining of, distal VHs, with patterns similar to those of "locus-contracted" primary pro-B cells. Thus, downmodulation of CTCF-bound scanning-impediment activity promotes cohesin-driven RAG-scanning across the 2.7Mb Igh locus.Cohesin is a highly conserved chromosome-associated multi-subunit ring-shaped ATPase complex built upon subunits belonging to the structural maintenance of chromosomes (Smc) family and is important for diverse chromosome-based processes [28][29][30][31][32][33] .The cohesin complex is proposed to form contact loop domains by extrusion of chromatin until reaching convergent CTCF-bound CBE anchors 2-10 . In this regard, cohesin extrudes both naked and nucleosome-containing DNA in an NIPBL-MAU2 and ATP-hydrolysisdependent manner in vitro 34,35 . Our studies implicated the cohesin complex in chromatin loop extrusion-mediated mechanisms of lymphocyte V(D)J and IgH class switch recombination 11,[14][15][16]36,37 . To further elucidate potential cohesin role(s) in chromatin scanning during long-range V(D)J recombination, we employed a mini auxin-inducible degron (mAID) approach 4,7,26,27 to conditionally degrade Rad21, a core component of the cohesin complex,in v-Abl-kinase-transformed, Eµ-Bcl2-expressing mouse pro-B cells ("v-Abl pro-B cells").

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“…These domains are on average 1Mb long (in mammals) and usually contain several gene domains. With the increase of the resolution of Hi-C maps, sub-TADs and even smaller micro-TADs have been identified within TADs [27,33,34]. These smaller contact domains would correspond to the gene domains as defined here.…”

Section: Gene Domains Can Be Physically Identified As Preferential Comentioning

confidence: 67%

The 3D Genome Shapes the Regulatory Code of Developmental Genes

Mozziconacci

Merle

Lesne

2020

Journal of Molecular Biology

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mots)We revisit the notion of gene regulatory code in embryonic development in the light of recent findings about genome spatial organisation. By analogy with the genetic code, we posit that the concept of code can only be used if the corresponding adaptor can clearly be identified. An adaptor is here defined as an intermediary physical entity mediating the correspondence between codewords and objects in a gratuitous and evolvable way. In the context of the gene regulatory code, the encoded objects are the gene expression levels, while the concentrations of specific transcription factors in the cell nucleus provide the codewords. The notion of code is meaningful in the absence of direct physicochemical relationships between the objects and the codewords, when the mediation by an adaptor is required. We propose that a plausible adaptor for this code is the gene domain, that is, the genome segment delimited by topological insulators and comprising the gene and its enhancer regulatory sequences. We review recent evidences, based on genome-wide chromosome conformation capture experiments, showing that preferential contact domains found in metazoan genomes are the physical traces of gene domains. Accordingly, genome 3D folding plays a direct role in shaping the developmental gene regulatory code.

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Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding

Cited by 499 publications

References 94 publications

Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning

The 3D Genome Shapes the Regulatory Code of Developmental Genes

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