During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological organization of Hox clusters and their transcriptional activation in space and time has served as a paradigm for understanding the relationships between genome structure and function. Here, we review some recent observations, which revealed highly dynamic changes in the structure of chromatin at Hox clusters, in parallel with their activation during embryonic development. We discuss the relevance of these findings for our understanding of large-scale gene regulation.
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http://dx.doi.org/10.1098/rstb.2012.0367 | DOI Listing |
Evol Lett
December 2024
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, United States.
The genetic mechanisms underlying striking axial patterning changes in wild species are still largely unknown. Previous studies have shown that fish, commonly known as fourspine sticklebacks, have evolved multiple different axial patterns in wild populations. Here, we revisit classic locations in Nova Scotia, Canada, where both high-spined and low-spined morphs are particularly common.
View Article and Find Full Text PDFJ Inherit Metab Dis
December 2024
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.
Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, required to metabolize the amino acids leucine, isoleucine, and valine. Despite its profound metabolic implications, the molecular alterations underlying this metabolic impairment had not yet been completely elucidated. We performed a comprehensive multi-omics integration analysis, including genomic, epigenomic, and transcriptomic data from fibroblasts derived from a cohort of MSUD patients and unaffected controls to genetically characterize an MSUD case and to unravel the MSUD pathophysiology.
View Article and Find Full Text PDFHum Cell
November 2024
Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, Room No. 401, 4th Floor, New Delhi, India.
Acute myeloid leukemia (AML) is characterized by impaired differentiation of myeloid cells leading to hematopoietic failure. Despite advances, the molecular mechanisms driving AML remain incompletely understood, limiting the identification and targeting of critical vulnerabilities in leukemic cells. Homeobox (HOX) genes, encoding transcription factors essential for myeloid and lymphoid differentiation, are distributed across four clusters: HOXA (chromosome 7), HOXB (chromosome 17), HOXC (chromosome 12), and HOXD (chromosome 2).
View Article and Find Full Text PDFSci Rep
November 2024
Institut für Zoologie, Universität zu Köln, Zülpicher str. 47b, 50674, Cologne, Germany.
Hox genes are central to metazoan body plan formation, patterning and evolution, playing a critical role in cell fate decisions early in embryonic development in invertebrates and vertebrates. While the archetypical Hox gene cluster consists of members of nine ortholog groups (HOX1-HOX9), arrayed in close linkage in the order in which they have their anterior-posterior patterning effects, nematode Hox gene sets do not fit this model. The Caenorhabditis elegans Hox gene set is not clustered and contains only six Hox genes from four of the ancestral groups.
View Article and Find Full Text PDFGenes (Basel)
November 2024
Laboratório de Toxicologia e Biologia Molecular, Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, RJ, Brazil.
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