Polycomb factor Phf19 controls cell growth and differentiation towards erythroid pathway in chronic myeloid leukemia cells

Polycomb group (PcG) of proteins are a group of highly conserved epigenetic regulators involved in many biological functions, such as embryonic development, cell proliferation and adult stem cell determination. PHD finger protein 19 (PHF19) is an associated factor of Polycomb Repressor Complex 2 (PRC2) up-regulated in different human cancers. In particular, myeloid leukemia cell lines show increased levels of PHF19, yet little is known about its function. Here, we have characterized the role of PHF19 in cell lines of a type of myeloid leukemia named chronic myeloid leukemia (CML). Thus, we have demonstrated that PHF19 depletion decreases cell proliferation and promotes differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through its epigenetic regulation of the cell cycle regulator p21. Furthermore, we have observed that MTF2, a PHF19 homolog, compensates at chromatin level for PHF19 depletion, instructing specific erythroid differentiation. Taken together, our results show that PHF19 is a key transcriptional regulator for cell fate determination and could be a potential target for myeloid leukemia treatment. ChIP-seq (6 samples with fly spike-in) of K562 cells. shCT means shRNA Control, sh1 and sh2 are two different knock-downs of PHF19 long isoform. RNA-seq (6 samples, 3 conditions with 2 replicates per condition) of K562 cells. shCT means shRNA Control, sh1 and sh2 are two different knock-downs of PHF19 long isoform.