Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells

Leucèmia mieloide crònica; Diferenciació eritroïdal; PolycombLeucemia mieloide crónica; Diferenciación eritroide; PolycombChronic myeloid leukemia; Erythroid differentiation; PolycombPolycomb 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.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 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 Fundación Científica de la Asociación Española Contra el Cáncer. SA was funded by the Ramon y Cajal program of the Ministerio de Ciencia, Innovación y Universidades, the European Social Fund under the reference number RYC-2018-025002-I, and the Instituto de Salud Carlos III-FEDER (PI19/01814)

Comparison of the thermal effect of two automatic controls of roller shutters in an academic space

Roller shutters are passive systems that can be operated automatically to improve building energy efficiency based on different criteria. This paper aims to compare the effect of an occupant-based and a thermal-based control of roller shutters on heating and cooling demand in an academic space. We run dynamic energy simulations of a case study in the Mediterranean climate (Barcelona, Spain). We found that the automatic control of roller shutters can significantly decrease heating and cooling demand. Both controls here analyzed perform similarly, with a rough reduction in heating of 1/2 and in cooling of 2/3. Therefore, occupant-based controls can be good alternatives that reduce energy demand as well as preserve occupants’ capacity to satisfy their needs or wills. Automated control of roller shutters could perform better if based on the energy balance of solar gains, thermal conduction and infiltration through the window. In addition to solar shading, the thermal insulation and infiltration-control provided by roller shutters are also key to improving building thermal performance in the Mediterranean climate.Peer ReviewedObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant::7.3 - Per a 2030, duplicar la taxa mundial de millora de l’eficiència energèticaObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (published version

The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation

Phf19, a Polycomb subunit, controls hematopoietic stem cells identity and differentiation. Adult hematopoietic stem cells (HSCs) are rare multipotent cells in bone marrow that are responsible for generating all blood cell types. HSCs are a heterogeneous group of cells with high plasticity, in part, conferred by epigenetic mechanisms. PHF19, a subunit of the Polycomb repressive complex 2 (PRC2), is preferentially expressed in mouse hematopoietic precursors. Here, we now show that, in stark contrast to results published for other PRC2 subunits, genetic depletion of Phf19 increases HSC identity and quiescence. While proliferation of HSCs is normally triggered by forced mobilization, defects in differentiation impede long-term correct blood production, eventually leading to aberrant hematopoiesis. At molecular level, PHF19 deletion triggers a redistribution of the histone repressive mark H3K27me3, which notably accumulates at blood lineage-specific genes. Our results provide novel insights into how epigenetic mechanisms determine HSC identity, control differentiation, and are key for proper hematopoiesis