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UMI-4C for quantitative and targeted chromosomal contact profiling

ABSTRACT: We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (UMI) to derive high complexity quantitative chromosome contact profiles with controlled signal to noise ratios. We demonstrate that the method improves the sensitivity and specificity for detection of long-range chromosomal interactions, and that it allows the design of interaction screens with predictable statistical power. UMI-4C robustly quantifies contact intensity changes between cell types and conditions, opening the way toward incorporation of long-range interactions in quantitative models of gene regulation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE87209 | GEO | 2016/09/23

SECONDARY ACCESSION(S): PRJNA343885

REPOSITORIES: GEO

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UMI-4C for quantitative and targeted chromosomal contact profiling

2016-06-15 | GSE76763 | GEO

UMI-4C for quantitative and targeted chromosomal contact profiling

Project description:We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (UMI) to derive high complexity quantitative chromosome contact profiles with controlled signal to noise ratios. We demonstrate that the method improves the sensitivity and specificity for detection of long-range chromosomal interactions, and that it allows the design of interaction screens with predictable statistical power. UMI-4C robustly quantifies contact intensity changes between cell types and conditions, opening the way toward incorporation of long-range interactions in quantitative models of gene regulation. We constructed UMI-4C profiles of 13 different genomic loci (viewpoints) in five different cell lines, in order to study the 3D chromatin contact maps of these selected loci. The coordinates for these viewpoints are: G1p1 chrX:48646542; baitG1_3_5kb chrX:48641393; bait_50kb chrX:48595987; bait_165kb chrX:48476525; ANK1 chr8:41654693; hbb_3HS chr11:5221346; hbb_HBB chr11:5248714; hbb_HBBP1_G1 chr11:5266532; HBB_HBE chr11:5292159; HBB_HS2 chr11:5301345; HBB_HS3 chr11:5306690; HBB_HS5 chr11:5313539; HBB_HBD chr11:5256597

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Project description:UMI-4C for quantitative and targeted chromosomal contact profiling

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UMI-4C in control and HASTER-deficient EndoC-betaH3 cells overexpressing HNF1A

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Project description:The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We have developed 4C technology, or 3C-on-chip, which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active b-globin locus in fetal liver contacts mostly transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, while the inactive locus in fetal brain contacts different, transcriptionally silent, loci. A housekeeping gene in a gene dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture. Keywords: 4C technology

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