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The interphase chromatin structure is extremely complex, precise and dynamic. Experimental methods can only show the frequency of interaction of the various parts of the chromatin. Therefore, it is extremely important to develop theoretical methods to predict the chromatin structure. In this publication, we implemented an extended version of the SBS model described by Barbieri et al. and created the ChroMC program that is easy to use and freely available (https://github.com/regulomics/chroMC) to other users. We also describe the necessary factors for the effective modeling of the chromatin structure in . We compared results of chromatin structure predictions using two methods: Monte Carlo and Molecular Dynamic. Our simulations suggest that incorporating black, non-reactive chromatin is necessary for successful prediction of chromatin structure, while the loop extrusion model with a long range attraction potential or Lennard-Jones (with local attraction force) as well as using Hi-C data as input are not essential for the basic structure reconstruction. We also proposed a new way to calculate the similarity of the properties of contact maps including the calculation of local similarity.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2023.2291176 | DOI Listing |
Mol Cell
December 2024
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:
How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements.
View Article and Find Full Text PDFiScience
December 2024
Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
As an essential regulator of higher-order chromatin structures, CCCTC-binding factor (CTCF) is a highly conserved protein with a central DNA-binding domain of 11 tandem zinc fingers (ZFs), which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with electrophoretic mobility shift assay (EMSA), circularized chromosome conformation capture (4C), qPCR, chromatin immunoprecipitation with sequencing (ChIP-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq), we uncovered a negatively charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility.
View Article and Find Full Text PDFMol Cell
December 2024
Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA; Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:
Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) OT Gatersleben, Corrensstr 3, 06466 Seeland, Germany.
In eukaryotes, accurate chromosome segregation during cell division relies on the centromeric histone H3 variant, CENH3. Our previous work identified KINETOCHORE NULL2 (αKNL2) as a plant CENH3 assembly factor, which contains a centromere-targeting motif, CENPC-k, analogous to the CENPC motif found in CENP-C. We also demonstrated that αKNL2 can bind DNA in vitro in a sequence-independent manner, without the involvement of its CENPC-k motif.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Sequencing-based Hi-C technology has been widely used to study the three-dimensional structure of chromatin. More recently, the development of single-cell Hi-C technology has enabled the study of chromatin structural variations between individual cells. However, single-cell Hi-C data are often highly sparse, necessitating the use of imputation algorithms to address insufficient sampling.
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