In all cell lines analyzed, including cells of lung, renal, monocytic and tcell origin, the irak2 luciferase reporter construct, containing an intact ctcf binding site, showed strong promoter activity. Abstractctcf is a highly conserved transcriptional regulator protein that performs diverse functions. Recent research has shown a role for ctcf in estrogen receptor er biology, at some individual loci, but a multicontext global analysis of ctcf binding and transcription activity is lacking. Lats kinasemediated ctcf phosphorylation and selective loss. Predicts whether a pair of convergent ccctc binding factor ctcf motifs can form a chromatin loop. Recent evidence has implicated a role for ctcf in regulating gene expression in the human mhcii locus. Mouse genome database mgd, gene expression database gxd, mouse.
Proteinligand binding and molecular recognition database. The database provides a simple web tool to search for the core ctcfbinding motifs in a query sequence. Ctcf mediated human 3d genome architecture reveals chromatin topology for transcription. Jaspar is an openaccess database of curated, nonredundant transcription factor tf binding profiles stored as position frequency matrices pfms and tf flexible models tffms for tfs across multiple species in six taxonomic groups. Mouse genome database mgd, gene expression database gxd, mouse models of human cancer database mmhcdb formerly mouse tumor biology mtb, gene ontology.
The insulator binding protein ctcf associates with the nuclear matrix. This unusual dna structure is formed at several ctcf binding sites and is formed in a directional manner. One interpretation of these data is that ctcf binds dxz4 at the xa and xi equally, but not detecting ctcf at dxz4 in all males even when it is readily detected in the same samples at a known ctcf binding site within the h19 imprinted control region 47, 48 suggests that binding of ctcf. Bindingdb is a public, webaccessible database of measured binding affinities, focusing chiefly on the interactions of protein considered to be drugtargets with small, druglike molecules. Starting from the peak profile downloaded from encode see extended data sheet, we identified the center of binding for each peak of both ctcf. The stressinduced ctcf phosphorylation and locusspecific dissociation from dna were latsdependent. Ctcf binding to the h19 sequence was inhibited by dna methylation at a single cpg site corresponding to the c 2 position. The ccctcbinding factor ctcf mediates transcriptional regulation and implicates epigenetic modifications in cancers. Resultswe now map ctcf binding genome wide in breast. The database provides a description of the binding site, where the binding sequence is. Ctcf modulates allelespecific subtad organization and. Dec 12, 2019 maternal allelespecific ctcf binding at the imprinted igf2h19 and the dlk1dio3 domains adds an additional layer of subtad organization, on top of an existing threedimensional configuration and prior to imprinted activation of proteincoding genes. Here, we describe recent updates to a database of ctcf binding sites, ctcfbsdb.
Each ctcfbinding sequence in the database is identified by a prefix containing information about the data source appended to a number, creating a unique identifier for each binding sequence. The multidomain ccctc binding factor ctcf, containing a tandem array of 11 zinc fingers zfs, modulates the threedimensional organization of chromatin. Topoisomerase ii beta interacts with cohesin and ctcf at. Ctcfbsdb, a database for ctcf binding sites and genome organization, database, website factorbook, a wikibased database for transcription. We crystallized the human ctcf dna binding domain in complex with a known ctcf binding site. Here, we describe recent updates to a database of ctcfbinding sites, ctcfbsdb, which now contains almost 15 million ctcfbinding. Ctcf binding sites were collected from published papers containing ctcf binding sites identified using chipseq or similar methods, data from the encode project, and a set of approximately 100 manually curated binding sites. However, the systematically unveiling inverse regulatory relationship. Structural basis for the versatile and methylation. Backgroundccctc binding factor ctcf is a conserved zinc finger transcription factor that is involved in both intra and interchromasomal looping. They showed that the human ctcf protein contains 11 zinc finger domains and is exceptionally highly conserved, sharing 93% identity with the avian ctcf amino acid sequence. The study suggests that external signals may rapidly modulate the 3d genome by affecting ctcf genomic binding. Ctcf binds to different dna sequences through combinatorial use of 11zinc.
Constitutively bound ctcf sites maintain 3d chromatin. Ctcf also plays a crucial role in the global organization of chromatic architecture. The database provides a description of the binding site, where the binding sequence is located within topological domains, and a genome browser viewer showing the genomic context of the binding. Functional signatures of evolutionarily young ctcf binding sites. This nuclear protein is able to use different combinations of the zf domains to bind different dna target sequences and proteins. Ccctcbinding factor ctcf and cohesin influence the genomic. Predicting ctcfmediated chromatin interactions by integrating. Ctcfbinding elements mediate accessibility of rag substrates. The evex database hdac1 and ctcf have a common binding. Data of epigenomic profiling of histone marks and ctcf binding sites in bovine rumen epithelial primary cells before and after butyrate treatment discovering the regulatory elements. This nuclear protein is able to use different combinations of the zf domains to bind.
This has been confirmed by mapping the presence of ccctc binding factor ctcf and smc1 using chipseq. Loss of ctcf binding disrupted local chromatin domains and downregulated genes located within them. The ccctcbinding zincfinger protein ctcfmediated network of. Ctcf and cmyc have a common binding partner sp1 cmyc binds with sp1 binding of sp1 and cmyc. During this process, vhproximal ctcf looping factor binding elements mediate greatly increased interactions of their associated vhs with the djh recombination center and, thereby, increase their accessibility for rag cleavage. To explore the bovine functional genomic elements and the vital roles of butyrate on the epigenetic modifications of bovine genomic activities, we generated and deposited the genomewide datasets of transcript factor binding sites of ctcf ccctc binding factor, insulator binding protein, histone methylation h3h27me3, h3k4me1, h3k4me3 and. Feb 05, 2014 the mammalian ccctc binding factor ctcf regulates gene expression through the formation of higher order chromatin structures. Additionally, the updated database includes new features enabled by new ctcfbinding site data, including binding site occupancy and the ability to visualize overlapping ctcfbinding sites determined in separate experiments.
Lats kinasemediated ctcf phosphorylation and selective. Currently, the database contains almost 15 million experimentally determined ctcf binding sites across several species. However, to date, proteins modulating the sitespecific interaction of ctcf with chromatin in mammalian cells has been lacking. Among the known ctcf binding partners, the cohesin complex in particular occupies a large fraction of ctcf sites in diverse cell types, and it participates in ctcf mediated insulator function parelho et al.
You are using the latest 8th release 2020 of jaspar. Oct 11, 2018 the ccctc binding zincfinger protein ctcf mediated network of longrange chromatin interactions is important for genome organization and function. Ctcf ccctc binding factor is the only known major insulator binding protein in the vertebrates and has been shown to bind many enhancerblocking elements. The typical workflows of data processing and integrative analysis with nuctools reveal information on the interplay of nucleosome positioning with other features such as for example binding of a transcription factor ctcf. Rna interactions are essential for ctcfmediated genome. The architectural protein ctcf is a mediator of chromatin conformation, but how ctcf binding to dna is orchestrated to maintain longrange gene expression is poorly. Wikigenes ctcf ccctcbinding factor zinc finger protein. Jaspar is the largest openaccess database of curated and nonredundant transcription factor tf binding profiles from six different taxonomic groups. The ctcf insulator protein forms an unusual dna structure. During this process, vhproximal ctcf looping factor binding elements mediate greatly increased interactions of their associated vhs with the djh recombination center and. Significance ccctc binding factor ctcf isan epigenetic regulatory protein that is not only functionally diverse, but is also targeted to highly diverse dna binding sites. An exceptionally conserved transcriptional repressor, ctcf, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian cmyc oncogenes. Currently, the database contains almost 15 million experimentally determined ctcf binding sequences across several species.
The mouse dxz4 homolog retains ctcf binding and proximity. Genomewide binding of posterior hoxad transcription factors. Gel shift assays of nuclear extracts from mouse and. Additionally, the updated database includes new features enabled by new ctcf binding site data, including binding site occupancy and the ability to visualize overlapping ctcf binding. Jaspar a database of transcription factor binding profiles.
The strand column in the bed output will tell you the direction of the motif. Ctcf binding sequences were collected from 12 published papers containing ctcf binding sites identified using chipseq or similar methods, data from the encode project, and a set of approximately 100 manually curated binding sites identified by lowthroughput experiments. This analysis validated the binding of ctcf to 80 95% tested sites supplemental figure 2a, and suggested a high degree of specificity of our method. Transcription factor binding site databases wikipedia. Matrixscl calculates combinatorial cooperative tfdna binding using transfer matrix formalism.
Systematical identification of cellspecificity of ctcf. Genomewide targeting of the epigenetic regulatory protein. To capture the formation of chromatin loops, we compiled a list of ctcf binding sites along the chromatin of interest using celltype specific chipseq data. Specifically, ctcf binding regions identified previously by the triple site analysis were scanned with the ctcf core motif. It includes integrated ctcf binding sites with genomic topological domains defined using hic data.
We crystallized the human ctcf dnabinding domain in complex with a known ctcfbinding site. Rag endonuclease associated with a djh recombination center is presented with upstream chromosomal vhs by a linear chromatin scanning process involving loop extrusion. Hdac1 and hdac2 are both found in multiprotein corepressor complexes sin3, nucleosomeremodeling hdac nurd and corest, which are recruited to chromatin regulatory regions by. The database provides a description of the binding site, where the binding sequence is located within topological domains, and a genome browser viewer showing the genomic context of the binding site. In fact, the binding of ctcf positively correlates with enhancer activity and deletion of ctcf sites compromises enhancerpromoter binding. Mar 23, 2007 to assess the accuracy of these in vivo ctcf binding sites, we first randomly selected 84 supplemental table 1 and performed conventional chip assays.
Ctcf is a dnabinding protein essential for the maintenance of genome architecture by mediating both short and longrange chromosomal contacts 11, 12. The bet protein brd2 cooperates with ctcf to enforce. Basic features of dnaproteindrug binding encountered in gene regulation include site specificity determined by the dna sequence, binding site overlapping, competitions between different protein types or different binding modes, cooperative interactions between proteins bound to the dna. Reactions were run on 2% agarose gels and analyzed using the imagelab software biorad. We used the storm program15 and each of the six pwm to report the single. Transcriptional repressor ctcf also known as 11zinc finger protein or ccctc binding factor is a transcription factor that in humans is encoded by the ctcf gene. The core of the integrative level of the encode encyclopedia is the registry of candidate regulatory elements cres, which integrates all highquality dnaseseq and h3k4me3, h3k27ac, and ctcf chipseq data. The multidomain ccctcbinding factor ctcf, containing a tandem array of 11 zinc fingers zfs, modulates the threedimensional organization of chromatin. Mutation hotspots at ctcf binding sites coupled to. Results from these analyses suggest that ctcf and cohesin are bound to the sperm genome in many of the same sites where these proteins are present in the genome of embryonic stem cells escs jung et al. We conclude that the ctcf insulator protein is able to form an unusual dna structure in vitro that we believe is a dna loop.
A role for ctcf and cohesin in subtelomere chromatin. Ctcf mp is a machine learning algorithm based on word2vec and boosted trees. Bindingdb contains 1,854,767 binding data, for 7,493 protein targets and 820,433 small molecules. The chipexo profiler method was used to generate top2b, ctcf and rad21 chipexoseq and dgf sequencing read profiles around the ctcf binding motif. Ctcf, ccctc binding factor vertebrate orthologs 10 human ortholog ctcf, ccctc binding factor. Ctcf is involved in many cellular processes, including transcriptional regulation, insulator activity, vdj recombination and regulation of chromatin architecture. We have developed the ctcf binding site database, a comprehensive collection of experimentally determined and computationally predicted ctcf binding sites ctcfbs. Ctcfbsdb is an online database that includes almost 15 million experimentally determined ctcf binding sites across several species. A coordinated interaction between ctcf and er in breast. Jerkovic i, ibrahim dm, andrey g, haas s, hansen p, janetzki c, et al. Here, using whole genome sequencing data from 212 gastric tumors, the authors identify recurring mutations at specific ctcf binding sites that are common across gastrointestinal cancers and. Ctcf is a highly conserved transcriptional regulator protein that performs diverse functions such as regulating gene expression and organizing the 3d structure of the genome. Gene name, ccctcbinding factor zinc finger protein. Jaspar is an openaccess database of curated, nonredundant transcription factor tf binding profiles stored as position frequency matrices pfms and tf flexible models tffms for tfs.
Chapter 4 identification and characterisation of binding sites. Graphs, graphs displaying summary information of all variants in the database. We analysed ctcf chipseq data for normal prostate cells prec and prostate cancer cell line lncap 16 and found that the ctcf binding pattern was strikingly similar across the locus regardless. Identification of genomic regulatory elements is essential for understanding the dynamics of. Predicting threedimensional genome organization with. Additionally, the updated database includes new features enabled by new ctcf binding site data, including binding site occupancy and the ability to visualize overlapping ctcf binding sites. It also offers important insights in the sequencebased features underlying loop formation between a pair of ctcf. Apr 18, 2018 here, using whole genome sequencing data from 212 gastric tumors, the authors identify recurring mutations at specific ctcf binding sites that are common across gastrointestinal cancers and. Second, a text search interface was developed for querying the database.
Maintenance of ctcf and transcription factormediated. D,top, the ctcf consensusbinding motif in reverse orientation from the jaspar database. Ag data commons providing central access to usdas open. It permits to evaluate the contributions of sequencebased features already encoded in the genome. Here, we describe recent updates to a database of ctcfbinding sites. One ctcfbinding site, conserved in mouse and human myc genes, was found immediately downstream of the major p2 promoter. It uses the storm program 33 to scan for each of the four pwm. Ding z, ni y, timmer sw, lee bk, battenhouse a, louzada s, et al. The study suggests that external signals may rapidly modulate the 3d genome by affecting ctcf genomic binding through zf linker phosphorylation. Pdf ctcfmediated human 3d genome architecture reveals. Ziebarth1,2, anindya bhattacharya1,2 and yan cui1,2, 1department of microbiology, immunology and. In this regard, we now report two independent features that disrupt ctcf association with chromatin. This article is from nucleic acids research, volume 41. Users can search for ctcfbinding sites by element name or by the pubmed identifier of the original literature.
Transfac databases were used to search for enrichment in ctcf binding sites. Here, we describe recent updates to a database of ctcfbinding sites, ctcfbsdb. Ctcfmediated human 3d genome architecture reveals chromatin. Analysis of the vertebrate insulator protein ctcf binding. We hypothesize that the loss of ctcf binding at the a allele in this locus would cause loss of ctcfmediated looping and, in turn, alter ccd structure.
It includes integrated ctcfbinding sites with genomic topological domains defined using hic data. The introduction of novel ctcf binding sites in gene regulatory regions. Data of epigenomic profiling of histone marks and ctcf binding sites in bovine rumen epithelial primary cells before and after butyrate treatment. Cohesin is colocalized with ctcf throughout the igh locus previously, we reported the locations of sites of ctcf binding throughout the igh locus using chipchip, and we confirmed that 10 of 10 sites within the igh locus also bound the cohesin subunit rad21, as determined by chip and quantitative pcr 9, 20.
709 367 1466 740 1002 863 929 1205 706 91 21 1599 124 1455 1325 722 1028 328 1523 1477 1526 1538 392 321 137 1195 1450 1295 1284 1445 855 761 262 1473 1501 424 359 7 1357 854 1395 111 925 1379 486 149 1401