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  • Articles  (5)
  • Latest Papers from Table of Contents or Articles in Press  (5)
  • Computational Methods, Chromatin and Epigenetics  (5)
  • 2020-2024
  • 2015-2019  (5)
  • Nucleic Acids Research  (5)
  • 134647
  • 60967
  • Biology  (5)
  • Medicine
  • 1
    Publication Date: 2017-01-10
    Description: ChIA-PET2 is a versatile and flexible pipeline for analyzing different types of ChIA-PET data from raw sequencing reads to chromatin loops. ChIA-PET2 integrates all steps required for ChIA-PET data analysis, including linker trimming, read alignment, duplicate removal, peak calling and chromatin loop calling. It supports different kinds of ChIA-PET data generated from different ChIA-PET protocols and also provides quality controls for different steps of ChIA-PET analysis. In addition, ChIA-PET2 can use phased genotype data to call allele-specific chromatin interactions. We applied ChIA-PET2 to different ChIA-PET datasets, demonstrating its significantly improved performance as well as its ability to easily process ChIA-PET raw data. ChIA-PET2 is available at https://github.com/GuipengLi/ChIA-PET2 .
    Keywords: Computational Methods, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2016-08-20
    Description: Linker histones are essential for DNA compaction in chromatin. They bind to nucleosomes in a 1:1 ratio forming chromatosomes. Alternative configurations have been proposed in which the globular domain of the linker histone H5 (gH5) is positioned either on- or off-dyad between the nucleosomal and linker DNAs. However, the dynamic pathways of chromatosome assembly remain elusive. Here, we studied the conformational plasticity of gH5 in unbound and off-dyad nucleosome-bound forms with classical and accelerated molecular dynamics simulations. We find that the unbound gH5 converts between open and closed conformations, preferring the closed form. However, the open gH5 contributes to a more rigid chromatosome and restricts the motion of the nearby linker DNA through hydrophobic interactions with thymidines. Moreover, the closed gH5 opens and reorients in accelerated simulations of the chromatosome. Brownian dynamics simulations of chromatosome assembly, accounting for a range of amplitudes of nucleosome opening and different nucleosome DNA sequences, support the existence of both on- and off-dyad binding modes of gH5 and reveal alternative, sequence and conformation-dependent chromatosome configurations. Taken together, these findings suggest that the conformational dynamics of linker histones and nucleosomes facilitate alternative chromatosome configurations through an interplay between induced fit and conformational selection.
    Keywords: Computational Methods, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2016-05-20
    Description: Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show that NFRs predicted by H3K4me1 and me3 patterns are associated with active enhancers and promoters, respectively. Furthermore, asymmetry in the height of peaks flanking the central valley can predict the directionality of stable transcription at promoters. Using PARE on ChIP-seq histone modifications from four ENCODE cell lines and four hematopoietic differentiation stages, we identified several enhancers whose regulatory activity is stage specific and correlates positively with the expression of proximal genes in a particular stage. In conclusion, our results demonstrate that PVP patterns delineate both the histone modification landscape and the transcriptional activities governed by active enhancers and promoters, and therefore can be used for their prediction. PARE is freely available at http://servers.binf.ku.dk/pare .
    Keywords: Computational Methods, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2016-03-19
    Description: DNA helical twist imposes geometric constraints on the location of histone–DNA interaction sites along nucleosomal DNA. Certain 10.5-bp periodic nucleotides in phase with these geometric constraints have been suggested to facilitate nucleosome positioning. However, the extent of nucleotide periodicity in nucleosomal DNA and its significance in directing nucleosome positioning still remain unclear. We clarify these issues by applying categorical spectral analysis to high-resolution nucleosome maps in two yeast species. We find that only a small fraction of nucleosomal sequences contain significant 10.5-bp periodicity. We further develop a spectral decomposition method to show that the previously observed periodicity in aligned nucleosomal sequences mainly results from proper phasing among nucleosomal sequences, and not from a preponderant occurrence of periodicity within individual sequences. Importantly, we show that this phasing may arise from the histones’ proclivity for putting preferred nucleotides at some of the evenly spaced histone–DNA contact points with respect to the dyad axis. We demonstrate that 10.5-bp periodicity, when present, significantly facilitates rotational, but not translational, nucleosome positioning. Finally, although periodicity only moderately affects nucleosome occupancy genome wide, reduced periodicity is an evolutionarily conserved signature of nucleosome-depleted regions around transcription start/termination sites.
    Keywords: Computational Methods, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2015-03-01
    Description: The large collections of ChIP-seq data rapidly accumulating in public data warehouses provide genome-wide binding site maps for hundreds of transcription factors (TFs). However, the extent of the regulatory occupancy space in the human genome has not yet been fully apprehended by integrating public ChIP-seq data sets and combining it with ENCODE TFs map. To enable genome-wide identification of regulatory elements we have collected, analysed and retained 395 available ChIP-seq data sets merged with ENCODE peaks covering a total of 237 TFs. This enhanced repertoire complements and refines current genome-wide occupancy maps by increasing the human genome regulatory search space by 14% compared to ENCODE alone, and also increases the complexity of the regulatory dictionary. As a direct application we used this unified binding repertoire to annotate variant enhancer loci (VELs) from H3K4me1 mark in two cancer cell lines (MCF-7, CRC) and observed enrichments of specific TFs involved in biological key functions to cancer development and proliferation. Those enrichments of TFs within VELs provide a direct annotation of non-coding regions detected in cancer genomes. Finally, full access to this catalogue is available online together with the TFs enrichment analysis tool ( http://tagc.univ-mrs.fr/remap/ ).
    Keywords: Computational Methods, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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