TY - JOUR
T1 - Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells
AU - García-Montolio, Marc
AU - Ballaré, Cecilia
AU - Blanco, Enrique
AU - Gutiérrez, Arantxa
AU - Aranda, Sergi
AU - Gómez, Antonio
AU - Kok, Chung H.
AU - Yeung, David T.
AU - Hughes, Timothy P.
AU - Vizán, Pedro
AU - Di Croce, Luciano
N1 - Funding Information:
This work was supported by the Di Croce Laboratory is supported by grants from the Spanish Ministry of Science and Innovation (BFU2016-75008-P and PID2019-108322GB-100), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (FEDER), and from AGAUR (SGR 2017-2019). We
Funding Information:
Funding. This work was supported by the Di Croce Laboratory is supported by grants from the Spanish Ministry of Science and Innovation (BFU2016-75008-P and PID2019-108322GB-100), ?Fundaci?n Vencer El Cancer? (VEC), the European Regional Development Fund (FEDER), and from AGAUR (SGR 2017-2019). We acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya. PV was supported by the Fundaci?n Cient?fica de la Asociaci?n Espa?ola Contra el C?ncer. SA was funded by the Ramon y Cajal program of the Ministerio de Ciencia, Innovaci?n y Universidades, the European Social Fund under the reference number RYC-2018-025002-I, and the Instituto de Salud Carlos III-FEDER (PI19/01814).
Publisher Copyright:
© Copyright © 2021 García-Montolio, Ballaré, Blanco, Gutiérrez, Aranda, Gómez, Kok, Yeung, Hughes, Vizán and Di Croce.
PY - 2021/4/29
Y1 - 2021/4/29
N2 - 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.
AB - 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.
KW - PHF19
KW - chronic myeloid leukemia
KW - epigenetics
KW - erythroid differentiation
KW - polycomb
UR - http://www.scopus.com/inward/record.url?scp=85105927243&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.655201
DO - 10.3389/fcell.2021.655201
M3 - Article
AN - SCOPUS:85105927243
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 655201
ER -
