Chromatin conformation signatures of cellular differentiation

Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir-William-Osler, Montréal, H3G1Y6, Canada.
Genome biology (Impact Factor: 10.47). 05/2009; 10(4):R37. DOI: 10.1186/gb-2009-10-4-r37
Source: PubMed

ABSTRACT One of the major genomics challenges is to better understand how correct gene expression is orchestrated. Recent studies have shown how spatial chromatin organization is critical in the regulation of gene expression. Here, we developed a suite of computer programs to identify chromatin conformation signatures with 5C technology We identified dynamic HoxA cluster chromatin conformation signatures associated with cellular differentiation. Genome-wide chromatin conformation signature identification might uniquely identify disease-associated states and represent an entirely novel class of human disease biomarkers.

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    Bioinformatics 09/2014; 30(17):i386-i392. DOI:10.1093/bioinformatics/btu443 · 4.62 Impact Factor
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    ABSTRACT: Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels.
    eLife Sciences 04/2014; 3:e02557. DOI:10.7554/eLife.02557.001 · 8.52 Impact Factor

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