[Analysis of epigenetic features of mouse Meckel's cartilage by integrating multi-omics data].

PURPOSE: To characterize the epigenetic features of mouse Meckel's cartilage and potential gene expression regulation mechanisms based on multi-omics data.

METHODS

E14.5 Meckel's cartilage and forelimb cartilage multi-omics data in our group were incorporated, and published datasets of a wide range of mouse chondrocytes from the GEO database were also downloaded. Bioinformatics methods were used to compare chromatin accessibility, histone acetylation modifications, as well as three-dimensional genomic structural differences between different chondrocyte samples.

RESULTS

ATAC-seq analysis results showed that E14.5 Meckel's cartilage exhibited a more similar chromatin accessibility pattern to epiphyseal cartilage. CUT-Tag analysis results showed that H3K27ac modification level of 11 899 peaks differed significantly between Meckel's cartilage and forelimb cartilage, and acetylation modifications in 8 572 peaks were upregulated in Merkel's cartilage. Motif analysis results showed that the up-regulated H3K27ac peaks in Meckel's cartilage were enriched with Fos, Atf3, and AP-1 binding sites. Integration analysis of CUT-Tag and Hi-C results indicated the presence of chromatin loop-mediated promoter-super-enhancer interactions at the loci of Runx2 and Six2.

CONCLUSIONS

E14.5 Meckel's cartilage mainly exhibits chromatin accessibility characteristics of proliferative chondrocytes. Transcription factors such as Fos, and Six2 may play an important role in the transcriptional regulation of Meckel's cartilage development during the proliferative stage. Changes in chromatin epigenetic modifications associated with hypertrophy of Meckel's cartilage may appear gradually during the later stage of Merkel's cartilage development.