Chromatin loops between gene pairs have been observed in diverse contexts in both flies and vertebrates. Combining high-resolution Capture-C, DNA fluorescence in situ hybridization, and genetic perturbations, we dissect the functional role of three loops between genes with related function during Drosophila embryogenesis. By mutating the loop anchor (but not the gene) or the gene (but not loop anchor), we disentangle loop formation and gene expression and show that the 3D proximity of paralogous gene loci supports their co-regulation. Breaking the loop leads to either an attenuation or enhancement of expression and perturbs their relative levels of expression and cross-regulation. Although many loops appear constitutive across embryogenesis, their function can change in different developmental contexts. Taken together, our results indicate that chromatin gene-gene loops act as architectural scaffolds that can be used in different ways in different contexts to fine-tune the coordinated expression of genes with related functions and sustain their cross-regulation.
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http://dx.doi.org/10.1016/j.molcel.2023.12.023 | DOI Listing |
Mol Cancer
September 2024
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Schizophr Res
August 2024
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Research Institute for Doping Control, Shanghai University of Sport, Shanghai 200438, China. Electronic address:
Schizophrenia is a polygenic complex disease with a heritability as high as 80 %, yet the mechanism of polygenic interaction in its pathogenesis remains unclear. Studying the interaction and regulation of schizophrenia susceptibility genes is crucial for unraveling the pathogenesis of schizophrenia and developing antipsychotic drugs. Therefore, we developed a bioinformatics method named GRACI (Gene Regulation Analysis based on Causal Inference) based on the principles of information theory, a causal inference model, and high order chromatin 3D conformation.
View Article and Find Full Text PDFNucleic Acids Res
February 2024
Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France.
The NF-κB protein p65/RelA plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA regulates gene transcription and alternative splicing through promoter enrichment and genomic exon occupancy, respectively. The intricate ways in which p65/RelA simultaneously governs these functions across various genes remain to be fully elucidated.
View Article and Find Full Text PDFMol Cell
March 2024
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany. Electronic address:
Chromatin loops between gene pairs have been observed in diverse contexts in both flies and vertebrates. Combining high-resolution Capture-C, DNA fluorescence in situ hybridization, and genetic perturbations, we dissect the functional role of three loops between genes with related function during Drosophila embryogenesis. By mutating the loop anchor (but not the gene) or the gene (but not loop anchor), we disentangle loop formation and gene expression and show that the 3D proximity of paralogous gene loci supports their co-regulation.
View Article and Find Full Text PDFCancer Biomark
January 2023
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Background: Lymphoid-specific helicase (HELLS), a SNF2-like chromatin-remodeling enzyme, plays a key role in tumor progression via its DNA methylation function. However, the effects of HELLS on immune infiltration and prognosis in liver hepatocellular carcinoma (LIHC) remain uncertain.
Methods: The Tumor Immune Estimation Resource (TIMER) database was employed to explore the pan-cancer mRNA expression of HELLS and its correlation with immunity.
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