2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
January 23rd, 2025
Version: 2
Max Planck Institute for Multidisciplinary Sciences
genomics
biorxiv

CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation during cellular differentiation

Karpinska, M. A.Open in Google Scholar•Zhu, Y.Open in Google Scholar•Fakhraei Ghazvini, Z.Open in Google Scholar•Ramasamy, S.Open in Google Scholar•Barbieri, M.Open in Google Scholar•Cao, N. T. B.Open in Google Scholar•Varahram, N.Open in Google Scholar•Aljahani, A.Open in Google Scholar•Lidschreiber, M.Open in Google Scholar•Papantonis, A.Open in Google Scholaret al.

Enhancers and promoters interact in 3D chromatin structures to regulate gene expression. Here, we characterize the mechanisms that drive the formation of these structures and their function in gene regulation in a lymphoid-to-myeloid transdifferentiation system. Based on analyses at base-pair resolution, we demonstrate a close correlation between binding of regulatory proteins, formation of chromatin interactions, and gene expression. Integration of multi-way interaction analyses and computational modeling shows that tissue-specific gene loci are organized into chromatin hubs, characterized by cooperative interactions between multiple enhancers, promoters, and CTCF-binding sites. Depletion of CTCF strongly impairs the formation of these structures. However, the effects of CTCF depletion on gene expression are modest and can be explained by rewired enhancer-promoter interactions. This demonstrates an instructive role for enhancer-promoter interactions in gene regulation that is independent of cooperative interactions in chromatin hubs. Together, these results contribute to a mechanistic understanding of the structure-function relationship of the genome during cellular differentiation.

Similar Papers

biorxiv
Thu Jan 23 2025
Evidence of inbreeding depression on stature in Brown Swiss cattle
Background Small effective population size and the disproportionately large use of few genetically superior bulls in artificial insemination lead to extensive runs of homozygosity and an increased risk of homozygosity for deleterious alleles in domestic cattle, which may cause inbreeding depression. The adverse effects of inbreeding on phenotypic performance are well established, but the genetic v...
He, Q.
•
Deuber, J.
•
Seefried, F.
•
Pausch, H.
•
Kadri, N.
biorxiv
Thu Jan 23 2025
Genomic adaptations to semi-aquatic and aquatic life in spiders
Spiders have primarily adapted to terrestrial life, yet a number of species have made evolutionary transitions to marine and freshwater environments. While its physiological and behavioral adaptations have been characterized, the genetic basis of semi-aquatic and aquatic adaptation in spiders remains poorly understood. Here, we provide a high-quality, chromosome-level genome assembly for the aquat...
Fan, Z.
•
Wang, L.-Y.
•
Luo, B.
•
Ren, T.-Y.
...•
Zhang, Z.-S.
biorxiv
Thu Jan 23 2025
Cell type-specific immune regulation under symbiosis in a facultatively symbiotic coral
Many cnidarians host single-celled algae within gastrodermal cells, yielding a mutually beneficial exchange of nutrients between host and symbiont, and dysbiosis can lead to host mortality. Previous research has uncovered symbiosis tradeoffs, including suppression of immune pathways in cnidarians hosting intracellular algae and correlations between symbiotic state and pathogen susceptibility. Here...
Valadez-Ingersoll, M.
•
Rivera, H. E.
•
Da-Anoy, J.
•
Kanke, M.
...•
Davies, S. W.
biorxiv
Wed Jan 22 2025
Discovery of single-stranded DNA in meteorite-derived cultures: evidence of novel genetic elements.
This study presents the first evidence of single-stranded DNA (ssDNA) sequences identified through shotgun metagenomic analysis of meteorite-derived cultures. These ssDNA sequences, predominantly isolated from the \"no-hits\" zone with no significant matches in existing genomic databases, exhibit conserved motifs, distinct secondary structural features, and a unique AT-rich composition. These char...
Lopez Ramon y Cajal, C.
biorxiv
Wed Jan 22 2025
Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans
Aging leads to the decline of immunity, rendering the elderly susceptible to infection and disease. In the CD8+ T cell compartment, aging leads to a substantial increase of cells with high levels of senescence-associated beta-galactosidase activity (SA-BGal) and other senescence characteristics, including a pro-inflammatory transcriptome and impaired proliferative potential. Using senescent cell i...
Turano, P. S.
•
Dewald, H. K.
•
Akbulut, E.
•
Vasilopoulos, T.
...•
Martinez Zamudio, R. I.
biorxiv
Wed Jan 22 2025
Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-driven β-cell gene expression defects
Pancreatic islets maintain glucose homeostasis through coordinated action of their constituent endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single cell transcriptome profiling of 245,878 human islet cells from a 48...
Bandesh, K.
•
Motakis, E.
•
Nargund, S.
•
Kursawe, R.
...•
Stitzel, M. L.
biorxiv
Wed Jan 22 2025
Comparative genomic analysis of a novel heat-tolerant and euryhaline strain of unicellular marine cyanobacterium Cyanobacterium sp. DS4 from a high-temperature lagoon
Background: Cyanobacteria have diversified through their long evolutionary history and occupy a wide range of environments on Earth. To advance our understanding of their adaption mechanisms in extreme environments, we performed stress tolerance characterizations, whole genome sequencing, and comparative genomic analyses of a novel heat-tolerant and euryhaline strain of the unicellular cyanobacter...
Chen, C.-N. N.
•
Lin, K.-M.
•
Lin, Y.-C.
•
Chang, H.-Y.
...•
Chu, H.-A.
biorxiv
Wed Jan 22 2025
Bioinformatic analysis reveals the molecular mechanisms of Trefoil factor 3 involved in asthma pathogenesis
Objective: Investigate the expression, regulatory network and function of TFF3 in asthma from a multi-omics perspective through bioinformatics and cellular experiments to provide clues for understanding its molecular mechanisms in asthma. Methods: Downloaded two asthma-related datasets (GSE67472 and GSE147878) from GEO. Conducted differential expression analysis and WGCNA to find common genes rela...
He, F.
•
Wang, S.
•
Huang, P.
•
Fan, X.
biorxiv
Wed Jan 22 2025
Genome-wide mapping of the Galleria mellonella larvae transcription start sites during fungal infection and treatment
Using Low Quantity single strand CAGE (LQ-ssCAGE), we mapped the transcription start sites (TSS). We annotated the 5\' end of the invertebrate Galleria mellonella, an upcoming and booming experimental model in infectious disease and immunology research. However, the current genome annotation of this model organism lacks annotation of the 5\' end and TSS information. G. mellonella larva was infecte...
Abugessaisa, I.
•
Konings, M.
•
Manabe, R.-i.
•
Tagami, M.
...•
Kasukawa, T.