Fifteen years ago, Lowary and Widom assembled nucleosomes on synthetic random sequence DNA molecules, selected the strongest nucleosomes and discovered that the TA dinucleotides in these strong nucleosome sequences often appear at 10-11 bases from one another or at distances which are multiples of this period. We repeated this experiment computationally, on large ensembles of natural genomic sequences, by selecting the strongest nucleosomes--i.e. those with such distances between like-named dinucleotides, multiples of 10.4 bases, the structural and sequence period of nucleosome DNA. The analysis confirmed the periodicity of TA dinucleotides in the strong nucleosomes, and revealed as well other periodic sequence elements, notably classical AA and TT dinucleotides. The matrices of DNA bendability and their simple linear forms--nucleosome positioning motifs--are calculated from the strong nucleosome DNA sequences. The motifs are in full accord with nucleosome positioning sequences derived earlier, thus confirming that the new technique, indeed, detects strong nucleosomes. Species- and isochore-specific variations of the matrices and of the positioning motifs are demonstrated. The strong nucleosome DNA sequences manifest the highest hitherto nucleosome positioning sequence signals, showing the dinucleotide periodicities in directly observable rather than in hidden form.
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http://dx.doi.org/10.1080/07391102.2013.855143 | DOI Listing |
Unlabelled: The cat eye syndrome chromosome region candidate 2 (CECR2) protein is an epigenetic regulator involved in chromatin remodeling and transcriptional control. The CECR2 bromodomain (CECR2-BRD) plays a pivotal role in directing the activity of CECR2 through its capacity to recognize and bind acetylated lysine residues on histone proteins. This study elucidates the binding specificity and structural mechanisms of CECR2-BRD interactions with both histone and non-histone ligands, employing techniques such as isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, and a high-throughput peptide assay.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
We theoretically investigate how the intranuclear environment influences the charge of a nucleosome core particle (NCP)-the fundamental unit of chromatin consisting of DNA wrapped around a core of histone proteins. The molecular-based theory explicitly considers the size, shape, conformation, charge, and chemical state of all molecular species-thereby linking the structural state with the chemical/charged state of the system. We investigate how variations in monovalent and divalent salt concentrations, as well as pH, affect the charge distribution across different regions of an NCP and quantify the impact of charge regulation.
View Article and Find Full Text PDFMol Cell
November 2024
Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics & Development, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:
Single-strand breaks (SSBs) are one of the most commonly occurring endogenous lesions with the potential to give rise to cytotoxic double-strand breaks (DSBs) during DNA replication. To investigate how replication-dependent DSBs are repaired, we employed Cas9 nickase (nCas9) to generate site- and strand-specific nicks in the budding yeast genome. We found that nCas9-induced nicks are converted to mostly double-ended DSBs during S phase.
View Article and Find Full Text PDFVirol J
November 2024
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology & Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.
Background: Viral infections are known to induce the occurrence and pathogenesis of systemic lupus erythematosus (SLE). Previous studies have indicated a possible relationship between SLE and human cytomegalovirus (HCMV) infection and have attributed HCMV to be associated with various autoantibodies; however, these studies were constrained by variations in sample size and potential selection bias. Therefore, in the present study, we aimed to elucidate the relationship between HCMV and autoantibodies in patients with SLE by integrating clinical data and genetic susceptibility.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
We theoretically investigate how the intranuclear environment influences the charge of a nucleosome core particle (NCP) - the fundamental unit of chromatin consisting of DNA wrapped around a core of histone proteins. The molecular-based theory explicitly considers the size, shape, conformations, charges, and chemical states of all molecular species - thereby linking the structural state with the chemical/charged state of the system. We investigate how variations in monovalent and divalent salt concentrations, as well as pH, affect the charge distribution across different regions of an NCP and quantify the impact of charge regulation.
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