Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes

Wuelling M. et al.

Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Microplex Library Preparation kit
True MicroChIP kit

Share this article

May, 2022


Products used in this publication

  • ChIP kit icon
    True MicroChIP kit
  • ChIP kit icon
    MicroPlex Library Preparation Kit v2 (12 indices)
  • chip kit icon
    MicroPlex Library Preparation Kit v3
  • cut and tag antibody icon
    H3K9me3 polyclonal antibody
  • ChIP-seq Grade
    H3K27me3 polyclonal antibody
  • ChIP-seq Grade
    H3K36me3 polyclonal antibody
  • cut and tag antibody icon
    H3K4me3 polyclonal antibody


  • EpiPlant 2024
    Clermont-Ferrand, France
    Jul 10-Jul 12, 2024


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy