Mammalian genomic DNA is packed in a small nucleus, and its folding and organization in the nucleus are critical for gene regulation and cell fate determination. In interphase, chromosomes are compartmentalized into certain nuclear spaces and territories that are considered incompatible with each other. The regulation of gene expression is influenced by the epigenetic characteristics of topologically associated domains and A/B compartments within chromosomes (intrachromosomal). Previously, interactions among chromosomes detected via chromosome conformation capture-based methods were considered noise or artificial errors. However, recent studies based on newly developed ligation-independent methods have shown that inter-chromosomal interactions play important roles in gene regulation. This review summarizes the recent understanding of spatial genomic organization in mammalian interphase nuclei and discusses the potential mechanisms that determine cell identity. In addition, this review highlights the potential role of inter-chromosomal interactions in early mouse development.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106443 | PMC |
http://dx.doi.org/10.3389/fcell.2024.1397807 | DOI Listing |
Nat Commun
December 2024
Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, 82152, Planegg-Martinsried, Germany.
The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Biochemistry and Molecular Biology, University Park, PA 16802, USA.
The genome-wide chromosome conformation capture method, Hi-C, has greatly advanced our understanding of genome organization. However, its quantitative properties, including sensitivity, bias, and linearity, remain challenging to assess. Measuring these properties is difficult due to the heterogenous and dynamic nature of chromosomal interactions.
View Article and Find Full Text PDFbioRxiv
September 2024
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Three-dimensional nuclear DNA architecture comprises well-studied intra-chromosomal () folding and less characterized inter-chromosomal () interfaces. Current predictive models of 3D genome folding can effectively infer pairwise -chromatin interactions from the primary DNA sequence but generally ignore contacts. There is an unmet need for robust models of -genome organization that provide insights into their underlying principles and functional relevance.
View Article and Find Full Text PDFCell Death Discov
August 2024
Department of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
J Hum Genet
October 2024
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Genome-wide association studies have enabled the identification of important genetic factors in many trait studies. However, only a fraction of the heritability can be explained by known genetic factors, even in the most common diseases. Genetic loci combinations, or epistatic contributions expressed by combinations of single nucleotide polymorphisms (SNPs), have been argued to be one of the critical factors explaining some of the missing heritability, especially in oligogenic/polygenic diseases.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!