Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells
Copyright policy )Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward 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), often upregulated in 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 myeloid leukemia cells. We demonstrated that PHF19 depletion decreases cell proliferation and promotes chronic myeloid leukemia (CML) differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through a direct regulation of the cell cycle inhibitor p21. Furthermore, we observed that MTF2, a PHF19 homolog, partially compensates for PHF19 depletion in a subset of target genes, 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 therapeutic target for myeloid leukemia treatment.
erythroid differentiation, epigenetics, Leucèmia mieloide crònica - Tractament, QH301-705.5, Other subheadings::Other subheadings::/therapy, Leucèmia, PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic, Cell and Developmental Biology, Otros calificadores::Otros calificadores::/terapia, FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica, chronic myeloid leukemia, Regulació genètica, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid, PHF19, Biology (General), polycomb, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide, Genètica
erythroid differentiation, epigenetics, Leucèmia mieloide crònica - Tractament, QH301-705.5, Other subheadings::Other subheadings::/therapy, Leucèmia, PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic, Cell and Developmental Biology, Otros calificadores::Otros calificadores::/terapia, FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica, chronic myeloid leukemia, Regulació genètica, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid, PHF19, Biology (General), polycomb, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide, Genètica
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