DNA-protein interactions play essential roles in all living cells. Understanding of how features embedded in the DNA sequence affect specific interactions with proteins is both challenging and important, since it may contribute to finding the means to regulate metabolic pathways involving DNA-protein interactions. Using a massive experimental benchmark dataset of binding scores for DNA sequences and a machine learning workflow, we describe the binding to DNA of T7 primase, as a model system for specific DNA-protein interactions. Effective binding of T7 primase to its specific DNA recognition sequences triggers the formation of RNA primers that serve as Okazaki fragment start sites during DNA replication.
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http://dx.doi.org/10.1093/nar/gkab956 | DOI Listing |
Nature
January 2025
Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.
View Article and Find Full Text PDFbioRxiv
January 2025
Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
View Article and Find Full Text PDFMol Ecol Resour
January 2025
National Research Collections Australia, Commonwealth Scientific Industrial Research Organisation, Canberra, Australian Capital Territory, Australia.
Formalin preservation of museum specimens has long been considered a barrier to molecular research due to extensive crosslinking and chemical modification. However, recent optimisation of hot alkaline lysis and proteinase K digestion DNA extraction methods have enabled a growing number of studies to overcome these challenges and conduct genome-wide re-sequencing and targeted locus-specific sequencing. The newest, and perhaps most unexpected utility of formalin preservation in archival samples is its ability to preserve in situ DNA-protein interactions at a molecular level.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Genes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
ChIP-Seq is used to study DNA-protein interactions, unraveling chromatin states and gene regulatory properties of transcription factors. ChIP-Seq involves immunoprecipitation followed by sequencing using Next-Generation sequencing approaches. The ENCODE consortium provides extensive guidelines for ChIP-Seq analysis.
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