Scientific article
OA Policy
English

Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development

Published inNature communications, vol. 15, no. 1, 4820
Publication date2024-06-06
First online date2024-06-06
Abstract

Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan -chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3 , Col2a1 , Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.

Keywords
  • Animals
  • Bone Development / genetics
  • Cell Differentiation / genetics
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrogenesis / genetics
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Enhancer Elements, Genetic / genetics
  • Extremities / embryology
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Male
  • Mice
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
Citation (ISO format)
DARBELLAY, Fabrice et al. Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development. In: Nature communications, 2024, vol. 15, n° 1, p. 4820. doi: 10.1038/s41467-024-49203-2

Technical informations

Creation14/10/2024 13:42:05
First validation04/11/2024 09:27:23
Update time04/11/2024 09:27:23
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