Publications by authors named "Landsman D"

The Clusters of Orthologous Genes (COG) database, originally created in 1997, has been updated to reflect the constantly growing collection of completely sequenced prokaryotic genomes. This update increased the genome coverage from 1309 to 2296 species, including 2103 bacteria and 193 archaea, in most cases, with a single representative genome per genus. This set covers all genera of bacteria and archaea that included organisms with 'complete genomes' as per NCBI databases in November 2023.

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  • FOXA1 and GATA4 are key pioneer factors that kickstart liver cell development by attaching to the N1 nucleosome in the ALB1 gene enhancer.
  • Cryo-electron microscopy was used to analyze the structures of the N1 nucleosome and its interactions with FOXA1 and GATA4, revealing how they bind to different parts of the nucleosome and work together.
  • The study indicates that FOXA1 enhances GATA4's ability to bind by repositioning the nucleosome, which helps regulate liver cell function-related genes by making the chromatin more accessible.
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Introduction: Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis.

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Wrapping of DNA into nucleosomes restricts accessibility to DNA and may affect the recognition of binding motifs by transcription factors. A certain class of transcription factors, the pioneer transcription factors, can specifically recognize their DNA binding sites on nucleosomes, initiate local chromatin opening, and facilitate the binding of co-factors in a cell-type-specific manner. For the majority of human pioneer transcription factors, the locations of their binding sites, mechanisms of binding, and regulation remain unknown.

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The cost and complexity of generating a complete reference genome means that many organisms lack an annotated reference. An alternative is to use a de novo reference transcriptome. This technology is cost-effective but is susceptible to off-target RNA contamination.

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Housekeeping genes are considered to be regulated by common enhancers across different tissues. Here we report that most of the commonly expressed mouse or human genes across different cell types, including more than half of the previously identified housekeeping genes, are associated with cell type-specific enhancers. Furthermore, the binding of most transcription factors (TFs) is cell type-specific.

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Wrapping of DNA into nucleosomes restricts accessibility to the DNA and may affect the recognition of binding motifs by transcription factors. A certain class of transcription factors, the pioneer transcription factors, can specifically recognize their DNA binding sites on nucleosomes, may initiate local chromatin opening and facilitate the binding of co-factors in a cell-type-specific manner. For the majority of human pioneer transcription factors, the locations of their binding sites, mechanisms of binding and regulation remain unknown.

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Histones have a long history of research in a wide range of species, leaving a legacy of complex nomenclature in the literature. Community-led discussions at the EMBO Workshop on Histone Variants in 2011 resulted in agreement amongst experts on a revised systematic protein nomenclature for histones, which is based on a combination of phylogenetic classification and historical symbol usage. Human and mouse histone gene symbols previously followed a genome-centric system that was not applicable across all vertebrate species and did not reflect the systematic histone protein nomenclature.

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Background: Disproportionate risks of COVID-19 in congregate care facilities including long-term care homes, retirement homes, and shelters both affect and are affected by SARS-CoV-2 infections among facility staff. In cities across Canada, there has been a consistent trend of geographic clustering of COVID-19 cases. However, there is limited information on how COVID-19 among facility staff reflects urban neighborhood disparities, particularly when stratified by the social and structural determinants of community-level transmission.

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Article Synopsis
  • A prodrome refers to the early signs or symptoms of a disease that appear before the main symptoms emerge, and is recognized in various conditions like Parkinson's and type 1 diabetes.
  • Recent findings suggest that multiple sclerosis (MS) also has a prodromal stage, which presents an opportunity for early intervention to potentially prevent or delay the onset of classical MS.
  • There is still much to learn about the prodromal stage of MS, so more research is necessary to establish clear criteria for identifying individuals at high risk for developing MS, which could aid in future treatment trials.
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Background: Nucleosomal binding proteins, HMGN, is a family of chromatin architectural proteins that are expressed in all vertebrate nuclei. Although previous studies have discovered that HMGN proteins have important roles in gene regulation and chromatin accessibility, whether and how HMGN proteins affect higher order chromatin status remains unknown.

Results: We examined the roles that HMGN1 and HMGN2 proteins play in higher order chromatin structures in three different cell types.

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Background: Multiple Sclerosis (MS) is a growing global health challenge affecting nearly 3 million people. Progress has been made in the understanding and treatment of MS over the last several decades, but cures remain elusive. The National MS Society is focused on achieving cures for MS.

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Cytosine methylation at the 5-carbon position is an essential DNA epigenetic mark in many eukaryotic organisms. Although countless structural and functional studies of cytosine methylation have been reported, our understanding of how it influences the nucleosome assembly, structure, and dynamics remains obscure. Here, we investigate the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability.

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We assessed the COVID-19 pandemic's impact on treatment of latent tuberculosis, and of active tuberculosis, at 3 centers in Montreal and Toronto, using data from 10 833 patients (8685 with latent tuberculosis infection, 2148 with active tuberculosis). Observation periods prior to declarations of COVID-19 public health emergencies ranged from 219 to 744 weeks, and after declarations, from 28 to 33 weeks. In the latter period, reductions in latent tuberculosis infection treatment initiation rates ranged from 30% to 66%.

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Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management.

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The Mediator complex is central to transcription by RNA polymerase II (Pol II) in eukaryotes. In budding yeast (), Mediator is recruited by activators and associates with core promoter regions, where it facilitates preinitiation complex (PIC) assembly, only transiently before Pol II escape. Interruption of the transcription cycle by inactivation or depletion of Kin28 inhibits Pol II escape and stabilizes this association.

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Little is known about the roles of histone tails in modulating nucleosomal DNA accessibility and its recognition by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full nucleosome, totaling 65 microseconds of molecular dynamics simulations. We observe rapid conformational transitions between tail bound and unbound states, and characterize kinetic and thermodynamic properties of histone tail-DNA interactions.

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Background: Inequities in the burden of COVID-19 were observed early in Canada and around the world, suggesting economically marginalized communities faced disproportionate risks. However, there has been limited systematic assessment of how heterogeneity in risks has evolved in large urban centers over time.

Purpose: To address this gap, we quantified the magnitude of risk heterogeneity in Toronto, Ontario from January to November 2020 using a retrospective, population-based observational study using surveillance data.

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Article Synopsis
  • Researchers studied how enhancers and promoters (regulatory DNA elements) form loops to regulate genes, focusing on enhancer strength indicated by binding of transcription factors.
  • They found that in active genomic regions (about 200-300 kb long), more active promoters correlate with fewer enhancers, suggesting an inverse relationship.
  • Using Hi-C analysis, they showed that these regulatory elements interact mainly in clusters, with a preference for being about 30 kb apart, leading to a new model describing their spatial organization as "transcription hubs" that resemble flower shapes.
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Background: Tuberculosis (TB) is a major cause of death worldwide. TB research draws heavily on clinical cohorts which can be generated using electronic health records (EHR), but granular information extracted from unstructured EHR data is limited. The St.

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Background: The NIH Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) initiative provides NIH-funded researchers cost-effective access to commercial cloud providers, such as Amazon Web Services (AWS) and Google Cloud Platform (GCP). These cloud providers represent an alternative for the execution of large computational biology experiments like transcriptome annotation, which is a complex analytical process that requires the interrogation of multiple biological databases with several advanced computational tools. The core components of annotation pipelines published since 2012 are BLAST sequence alignments using annotated databases of both nucleotide or protein sequences almost exclusively with networked on-premises compute systems.

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Background: FAIR (Findability, Accessibility, Interoperability, and Reusability) next-generation sequencing (NGS) data analysis relies on complex computational biology workflows and pipelines to guarantee reproducibility, portability, and scalability. Moreover, workflow languages, managers, and container technologies have helped address the problem of data analysis pipeline execution across multiple platforms in scalable ways.

Findings: Here, we present a project management framework for NGS data analysis called PM4NGS.

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Here, we present the data of human histone interactomes generated and analysed in the research article by Peng et al., 2020 [1]. The histone interactome data provide a comprehensive mapping of human histone/nucleosome interaction networks by using different data sources from the structural, chemical cross-linking, and high-throughput studies.

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Histone tails, representing the N-terminal or C-terminal regions flanking the histone core, play essential roles in chromatin signaling networks. Intrinsic disorder of histone tails and their propensity for post-translational modifications allow them to serve as hubs in coordination of epigenetic processes within the nucleosomal context. Deposition of histone variants with distinct histone tail properties further enriches histone tails' repertoire in epigenetic signaling.

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The Clusters of Orthologous Genes (COG) database, also referred to as the Clusters of Orthologous Groups of proteins, was created in 1997 and went through several rounds of updates, most recently, in 2014. The current update, available at https://www.ncbi.

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