A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.
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http://dx.doi.org/10.1073/pnas.0408952102 | DOI Listing |
Cells Dev
December 2024
Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, Paris, France; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
2024 not only marked the 100th anniversary of the discovery of the organizer by Hilde Pröscholdt-Mangold and Hans Spemann, but also the 40th anniversary of the discovery of the homeobox, a DNA region encoding a DNA binding peptide present in several transcription factors of critical importance for the gastrulating embryo. In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years, the study of their coordinated regulation in various contexts has progressively revealed their surprising regulatory strategies, based on mechanisms acting in-cis, which can translate a linear distribution of series of genes along the chromatin fiber into the proper sequences of morphologies observed along our various body axes.
View Article and Find Full Text PDFSci Rep
December 2024
Centre de Recherche sur le Cancer de L'Université Laval, Centre de Recherche du CHU de Québec-Université Laval (Oncology), 1401, 18e Rue, Québec, QC, G1J 1Z4, Canada.
Hoxa5 plays numerous roles in development, but its downstream molecular effects are mostly unknown. We applied bulk RNA-seq assays to characterize the transcriptional impact of the loss of Hoxa5 gene function in seven different biological contexts, including developing respiratory and musculoskeletal tissues that present phenotypes in Hoxa5 mouse mutants. This global analysis revealed few common transcriptional changes, suggesting that HOXA5 acts mainly via the regulation of context-specific effectors.
View Article and Find Full Text PDFGenes Dev
December 2024
Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA.
The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene orchestrates pan-neuronal gene expression throughout the nervous system of As in many other species, including humans, is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 ("CASP of nematodes") in How gene expression from this complex locus is controlled-and, in , directed to all cells of the nervous system-has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the homolog of vertebrate CELF proteins. During embryogenesis, the locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system.
View Article and Find Full Text PDFDev Growth Differ
December 2024
Graduate School of Medical Sciences, Tottori University Yonago, Tottori, Japan.
5'Hox genes regulate pattern formation along the axes of the limb. Previously, we showed that Hoxa13/Hoxd13 double-mutant newts lacked all digits of the forelimbs during development and regeneration, showing that newt Hox13 is necessary for digit formation in development and regeneration. In addition, we found another unique phenotype.
View Article and Find Full Text PDFOxid Med Cell Longev
December 2024
Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Mexico, Mexico.
Occupational exposure to arsenic (As), cadmium (Cd), and lead (Pb) affects many sectors, necessitating research to understand their transformation mechanisms. In this study, we characterized the process of epithelial-mesenchymal transition (EMT) in a rat hepatic epithelial cell line with decreased expression of catalase and glutamate cysteine ligase catalytic (GCLC) subunit that was exposed to a mixture of As, Cd, and Pb at equimolar occupational exposure concentrations. We evaluated the expression of genes and proteins involved in EMT.
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