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  1. Article ; Online: Large domains of heterochromatin direct the formation of short mitotic chromosome loops

    Maximilian H Fitz-James / Pin Tong / Alison L Pidoux / Hakan Ozadam / Liyan Yang / Sharon A White / Job Dekker / Robin C Allshire

    eLife, Vol

    2020  Volume 9

    Abstract: During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other ... ...

    Abstract During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.
    Keywords chromosome structure ; heterochromatin ; condensin ; loop extrusion ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome

    Michal R. Gdula / Tatyana B. Nesterova / Greta Pintacuda / Jonathan Godwin / Ye Zhan / Hakan Ozadam / Michael McClellan / Daniella Moralli / Felix Krueger / Catherine M. Green / Wolf Reik / Skirmantas Kriaucionis / Edith Heard / Job Dekker / Neil Brockdorff

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, ...

    Abstract The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome

    Michal R. Gdula / Tatyana B. Nesterova / Greta Pintacuda / Jonathan Godwin / Ye Zhan / Hakan Ozadam / Michael McClellan / Daniella Moralli / Felix Krueger / Catherine M. Green / Wolf Reik / Skirmantas Kriaucionis / Edith Heard / Job Dekker / Neil Brockdorff

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, ...

    Abstract The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Measuring the reproducibility and quality of Hi-C data

    Galip Gürkan Yardımcı / Hakan Ozadam / Michael E. G. Sauria / Oana Ursu / Koon-Kiu Yan / Tao Yang / Abhijit Chakraborty / Arya Kaul / Bryan R. Lajoie / Fan Song / Ye Zhan / Ferhat Ay / Mark Gerstein / Anshul Kundaje / Qunhua Li / James Taylor / Feng Yue / Job Dekker / William S. Noble

    Genome Biology, Vol 20, Iss 1, Pp 1-

    2019  Volume 19

    Abstract: Abstract Background Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple ...

    Abstract Abstract Background Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. Results Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established measures, such as the ratio of intra- to interchromosomal interactions, and novel ones, such as QuASAR-QC, to identify low-quality experiments. Conclusions In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available at http://github.com/kundajelab/3DChromatin_ReplicateQC to facilitate adoption in the community.
    Keywords Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Subject code 612
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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