Somitogenesis requires a segmentation clock and Notch signaling. Lunatic fringe (Lfng) expression in the presomitic mesoderm (PSM) cycles in the posterior PSM, is refined in the segmenting somite to the rostral compartment, and is required for segmentation. We identify distinct cis-acting regulatory elements for each aspect of Lfng expression. Fringe clock element 1 (FCE1) represents a conserved 110 bp region that is necessary to direct cyclic Lfng RNA expression in the posterior PSM. Mutational analysis of E boxes within FCE1 indicates a potential interplay of positive and negative transcriptional regulation by cyclically expressed bHLH proteins. A separable Lfng regulatory region directs expression to the prospective rostral aspect of the condensing somite. These independent Lfng regulatory cassettes advance a molecular framework for deciphering somite segmentation.
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http://dx.doi.org/10.1016/s1534-5807(02)00212-5 | DOI Listing |
Nat Commun
January 2025
MRC Laboratory of Medical Sciences, London, UK.
Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.
View Article and Find Full Text PDFGenes Dev
January 2025
Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center Utrecht, Utrecht 3584 CT, the Netherlands;
Enhancers are tissue-specific regulatory DNA elements that can activate transcription of genes over distance. Their target genes most often are located in the same contact domain-chromosomal entities formed by cohesin DNA loop extrusion and typically flanked by CTCF-bound boundaries. Enhancers shared by multiple unrelated genes are underexplored but may be more common than anticipated.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616.
The L-type Ca channel (Ca1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca flux that drives Ca-induced-Ca-release, Ca1.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China.
Recent studies have demonstrated that chronic stress can enhance the development of multiple human diseases, including cancer. However, the role of chronic stress in esophageal carcinogenesis and its underlying molecular mechanisms remain unclear. This study uncovered that dysregulated cholesterol metabolism significantly promotes esophageal carcinogenesis under chronic stress conditions.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors.
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