Finally, we found that the EZH2-LIN28B-CDK6 axis leads to increased resistance to the CDK4/6 inhibitor palbociclib. 13/17

Secondly, as observed in the Hi-C, these peaks are found in regions where there is high DNA-DNA contact frequency in all conditions, suggesting H3K27me3 is preferentially maintained at these hubs of compacted chromatin ➰➰➰. 9/17

Naturally, we observed that some level of H3K27me3 is maintained in EZH2+/- and we found out that these maintained me3 peaks show distinctive characteristics. Firstly, these peaks are wider, covering a larger genomic area🧬. 8/17

Again, we observed that regions with increased accessibility were enriched for GO terms relating to cell differentiation and alternative transcriptional lineages. 6/17

As expected, we observed genome-wide decrease in the PRC2-mark H3K27me3, accompanied by increased H3K27ac and increased chromatin accessibility. NOTE: C5 and C9 are EZH2+/- cells in the figure below. 5/17

Strikingly, we observed that at the transcriptomic level the PRC2-depleted showed increased expression of genes typically expressed monocytic-dendritic progenitors (e.g., CDCA7, CDK6), and decreased expression of genes expressed in mature monocytes (e.g., ITGAM, S100A12)🩸. 3/17

We generated a PRC2-depleted model by heterozygously targeting the catalytic component EZH2✍️in OCI-AML2 cells🧫. We then extensively characterized these cells by RNA-Seq, ATAC-Seq, CUT&RUN and Hi-C. 2/17