GSE135029
Domain model explain propagation dynamics and stability of K27 and K36 methylation landscapes
Chromatin states must be stably maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications across cell division is thought to be central in this process. However, the histone modification landscape is challenged by the incorporation new unmodified histones during each cell cycle and the principles that govern heritability remain poorly defined. Here, we take a quantitative approach and develop a reusable computational model that describes propagation of K27 and K36 methylation states. We measure combinatorial K27 and K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones in the presence and absence of enzymatic inhibition. Our modelling rejects active global demethylation and invoke the existence of 8 domains defined by distinct methylation endpoints. We find that K27me3 on pre-existing histones stimulates the rate of de novo K27me3 establishment, supporting a read-write mechanism in timely chromatin restoration. Finally, we provide a detailed, quantitative picture of the mutual antagonism between K27 and K37 methylation, and propose that this antagonism enhance the stability of epigenetic states across cell division. Overall design: Quantitative ChIP-seq analysis of H3K36me2 and H3K27me3 distribution and abundance upon 7 days treatment with DMSO or EZH2 inhibitor (EPZ-6438) in E14 mESCs cells. All experiments were done in duplicates. Chromatin of Drosophila melanogater S2 cells were used as spike-in for normalization purpose. Standard ChIPseq was performed on the same cells for H3K36me3, H3K27me1, H3K27me2 and H3K27me3 to determine regions of enrichment for each of the marks.