Payne et al. (2020) combine in situ imaging and ex situ sequencing via spatially resolved unique molecular barcodes to query higher-order genome folding patterns in intact single nuclei from mouse embryos and human fibroblasts.
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http://dx.doi.org/10.1016/j.molcel.2021.02.035 | DOI Listing |
Hum Mol Genet
January 2025
Department of Human Genetics, McGill University, 3666 McTavish Street, Montreal, QC H3A 1Y2, Canada.
Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
The spatial organization of the genome plays a critical role in regulating gene expression, cellular differentiation, and genome stability. This review provides an in-depth examination of the methodologies, computational tools, and frameworks developed to map the three-dimensional (3D) architecture of the genome, focusing on both ligation-based and ligation-free techniques. We also explore the limitations of these methods, including biases introduced by restriction enzyme digestion and ligation inefficiencies, and compare them to more recent ligation-free approaches such as Genome Architecture Mapping (GAM) and Split-Pool Recognition of Interactions by Tag Extension (SPRITE).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Apurinic/apyrimidinic (AP) sites are endogenous DNA lesions widespread in human cells. Having no nucleobases, they are noncoding and promutagenic. AP site repair is generally initiated through strand incision by AP endonuclease 1 (APE1).
View Article and Find Full Text PDFJ Chem Phys
January 2025
Department of Physics and Astronomy and Center for Quantitative Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia.
Background/objectives: The ~1.6 kb NBPF repeat units in neuroblastoma breakpoint family (NBPF) genes are specific to humans and are associated with cognitive capacity in higher primates. While the number of NBPF monomers/Olduvai sequences in humans is approximately 2-3 times greater than in great apes, the difference in copy number values of canonical NBPF 3mer Higher-order repeats (HORs)/Olduvai triplets between humans and great apes is substantially larger.
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