Practical Analysis of Hi-C Data: Generating A/B Compartment Profiles

Miura, Hisashi; Poonperm, Rawin; Takahashi, Saori; Hiratani, Ichiro

doi:10.1007/978-1-4939-8766-5_16

Cited by 27 publications

(20 citation statements)

References 48 publications

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“…We used mapped reads with MAPQ > 30 to generate.hic files for further analyses. For generating A/B compartment profiles at 250-kb resolution, the first eigenvector of the Pearson’s correlation matrix was used 64 . For the analysis of the differences in the Hi-C contact frequency, we extracted the number of interactions (i.e., reads) revealed by Hi-C for every 250-kb bin using the Juicer tools 63 from the hic file, and the differences in the interaction frequencies on chr6 (chr6:100,000,000–155,000,000) were calculated using the R package HiCcompare 65 .…”

Section: Methodsmentioning

confidence: 99%

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

et al. 2019

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MCF7 cells acquire estrogen-independent proliferation after long-term estrogen deprivation (LTED), which recapitulates endocrine therapy resistance. LTED cells can become primed for apoptosis, but the underlying mechanism is largely unknown. We previously reported that Eleanor non-coding RNAs (ncRNAs) upregulate the ESR1 gene in LTED cells. Here, we show that Eleanors delineate the topologically associating domain (TAD) of the ESR1 locus in the active nuclear compartment of LTED cells. The TAD interacts with another transcriptionally active TAD, which is 42.9 Mb away from ESR1 and contains a gene encoding the apoptotic transcription factor FOXO3. Inhibition of a promoter-associated Eleanor suppresses all genes inside the Eleanor TAD and the long-range interaction between the two TADs, but keeps FOXO3 active to facilitate apoptosis in LTED cells. These data indicate a role of ncRNAs in chromatin domain regulation, which may underlie the apoptosis-prone nature of therapy-resistant breast cancer cells and could be good therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

et al. 2019

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“…Principles of genome folding have been uncovered using Hi-C techniques, and the organization into two main structural and functional compartments, termed A and B, is apparent. Technically, A/B compartments are determined by a principal component analysis of normalized Hi-C data contact matrices [63, 65] (Fig. 2b).…”

Section: Spatial Organization Of the Genomementioning

confidence: 99%

Circadian rhythms in the three-dimensional genome: implications of chromatin interactions for cyclic transcription

2019

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Circadian rhythms orchestrate crucial physiological functions and behavioral aspects around a day in almost all living forms. The circadian clock is a time tracking system that permits organisms to predict and anticipate periodic environmental fluctuations. The circadian system is hierarchically organized, and a master pacemaker located in the brain synchronizes subsidiary clocks in the rest of the organism. Adequate synchrony between central and peripheral clocks ensures fitness and potentiates a healthy state. Conversely, disruption of circadian rhythmicity is associated with metabolic diseases, psychiatric disorders, or cancer, amongst other pathologies. Remarkably, the molecular machinery directing circadian rhythms consists of an intricate network of feedback loops in transcription and translation which impose 24-h cycles in gene expression across all tissues. Interestingly, the molecular clock collaborates with multitude of epigenetic remodelers to fine tune transcriptional rhythms in a tissue-specific manner. Very exciting research demonstrate that three-dimensional properties of the genome have a regulatory role on circadian transcriptional rhythmicity, from bacteria to mammals. Unexpectedly, highly dynamic long-range chromatin interactions have been revealed during the circadian cycle in mammalian cells, where thousands of regulatory elements physically interact with promoter regions every 24 h. Molecular mechanisms directing circadian dynamics on chromatin folding are emerging, and the coordinated action between the core clock and epigenetic remodelers appears to be essential for these movements. These evidences reveal a critical epigenetic regulatory layer for circadian rhythms and pave the way to uncover molecular mechanisms triggering pathological states associated to circadian misalignment.

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“…CscoreTool (Zheng and Zheng 2018 ) instead is not based on PCA to call compartments, but relies on a faster and memory efficient approach defining a compartment score reflecting the chance of any given bin to be in the “A” compartment. A detailed guide for the identification and annotation of compartments is reported in (Miura et al 2018 ).…”

Section: Downstream Analysesmentioning

confidence: 99%

“…Finally, an attempt to create a suite of tools for formats conversion, manipulation, and 2D genomic arithmetic of Hi-C data (similar to bedtools) is pgltools which is based on the paired-genomic-loci data (PGL) format (Greenwald et al 2017 ). Converting between these formats is not always straightforward and may require several steps (see examples in Miura et al ( 2018 )). For example, Juicer provides utilities to convert “.hic” files into sparse matrices, but to convert sparse or dense matrices into “.hic” files an intermediate text format is required.…”

Section: Handling Hi-c Data—data Formats and Tools For High-resolutiomentioning

confidence: 99%

Hi-C analysis: from data generation to integration

2018

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In the epigenetics field, large-scale functional genomics datasets of ever-increasing size and complexity have been produced using experimental techniques based on high-throughput sequencing. In particular, the study of the 3D organization of chromatin has raised increasing interest, thanks to the development of advanced experimental techniques. In this context, Hi-C has been widely adopted as a high-throughput method to measure pairwise contacts between virtually any pair of genomic loci, thus yielding unprecedented challenges for analyzing and handling the resulting complex datasets. In this review, we focus on the increasing complexity of available Hi-C datasets, which parallels the adoption of novel protocol variants. We also review the complexity of the multiple data analysis steps required to preprocess Hi-C sequencing reads and extract biologically meaningful information. Finally, we discuss solutions for handling and visualizing such large genomics datasets.

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Practical Analysis of Hi-C Data: Generating A/B Compartment Profiles

Cited by 27 publications

References 48 publications

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

Circadian rhythms in the three-dimensional genome: implications of chromatin interactions for cyclic transcription

Hi-C analysis: from data generation to integration

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