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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

HOXA cluster gene expression during osteoblast differentiation involves epigenetic control

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Author(s):
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da Silva, Rodrigo A. [1, 2] ; Fuhler, Gwenny M. [1] ; Janmaat, Vincent T. ; Fernandes, Cello Junior da C. [2] ; Feltran, Georgia da Silva [2] ; Oliveira, Flavia Amadeu [3] ; Matos, Adriana Arruda [3] ; Oliveira, Rodrigo Cardoso [3] ; Ferreira, Marcel Rodrigues [2] ; Zambuzzi, Willian F. [2] ; Peppelenbosch, Maikel P. [1]
Total Authors: 11
Affiliation:
[1] Erasmus MC, Univ Med Ctr Rotterdam, Dept Gastroenterol & Hepatol, Rotterdam - Netherlands
[2] Sao Paulo State Univ UNESP, Inst Biosci, Dept Chem & Biochem, Lab Bioassays & Cellular Dynam, BR-18618970 Botucatu, SP - Brazil
[3] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Al Octavio Pinheiro Brisolla 9-75, BR-17012901 Bauru, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BONE; v. 125, p. 74-86, AUG 2019.
Web of Science Citations: 3
Abstract

The HOXA gene cluster is generally recognized as a pivotal mediator of positional identity in the skeletal system, expression of different orthologues conferring alternative locational phenotype of the vertebrate bone. Strikingly, however, the molecular mechanisms that regulate orthologue-specific expression of different HOXA cluster members in gestating osteoblasts remain largely obscure, but in analogy to the processes observed in acute lymphatic leukemia it is assumed that alternative methylation of HOXA promoter regions drives position specific expression patterns. In an effort to understand HOXA cluster gene expression in osteogenesis we characterize both expression and the epigenetic landscape of the HOXA gene cluster during in vitro osteoblast formation from mesenchymal precursors. We observe that osteoblast formation per se provokes strong upregulation of HOXA gene cluster expression, in particular of midcluster genes, and paradoxal downregulation of HOXA7 and HOXA10. These differences in expression appear related to promoter methylation. LnRNAs HOTAIR and HOTTIP, known to modulate HOXA expression, are also regulated by their promoter methylation processing, but do not correlate with HOXA cluster expression profile. We thus conclude that HOXA expression is profoundly regulated during osteoblast differentiation through canonical methylation-dependent mechanisms but not through the flanking lnRNAs. (AU)

FAPESP's process: 16/01139-0 - Epigenetic modulation triggered by paracrine factors from endothelial cells on osteoblast
Grantee:Rodrigo Augusto da Silva
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
Grantee:Willian Fernando Zambuzzi
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 17/01046-5 - secRNA and DNA-methylome of osteoblast cells in response to paracrine effects od endothelial cells under a static and dynamic model.
Grantee:Rodrigo Augusto da Silva
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor