Fig. 3

Chromatin state transitions in promoters of differentially expressed genes during the cell transformation process and integration of epigenetic data (chromatin state clusters) with transcriptome dynamics (co-expression pathways). a Hierarchical clustering of transcripts based on enrichment of histone modifications and RNA Pol II at the promoter of DEGs. The color represents the median enrichment for each cluster of genes within ±1.5 kb of a TSS of a DEG. b Heat map illustrating the prevalence of chromatin state clusters in particular co-expression paths. The color represents Pearson residuals. Yellow indicates significant enrichment of transcripts in the corresponding expression pathways with a corresponding chromatin state cluster. c Biological process-based Gene Ontology analysis of chromatin state clusters, regrouped by hierarchical clustering (hierarchical tree in a), and associated with the same co-expression pathway. d Three examples of chromatin state clusters illustrating the evolution of the epigenetic landscape in the stepwise transformation process (black arrows in a). Panel 1 correspond to the changes from the bivalent chromatin state in BJ cells to the active state in BJEL and BJELM cells. In the same manner, panel 2 corresponds to the changes from the bivalent chromatin state in BJ and BJEL cells to the active state in BJELM cells. Finally, panel 3 corresponds to the chromatin state cluster that characterizes the group of downregulated genes in BJEL and BJELM cells; the promoters of these genes are in the active state in BJ cells but lose all marks in the BJEL and BJELM cells