30,112 research outputs found
The granulocytic inducer C/EBPalpha inactivates the myeloid master regulator PU.1
No full textVerschiedene Transkriptionsfaktoren spielen eine Rolle in der Entwicklung myeloischer Zellen. PU.1, ein Transkriptionsfaktor aus der ETS-Familie, ist sowohl für die Entwicklung lymphatischer als auch für die Entwicklung myeloischer Zellen von Bedeutung. Der Transkriptions
faktor C/EBPalpha, ein an den CCAAT-Enhancer bindendes Protein, ist hingegen wesentlich verantwortlich für die Entwicklung von Granulozyten. Wir stellen hier den ersten Nachweis dafür vor, dass C/EBPalpha die Funktion von PU.1 blockiert. PU.1 und C/EBPalpha können einander binden und sind in myeloischen Zellen kolokalisiert. Wenn C/EBPalpha PU.1 bindet, kann PU.1 einen minimalen Promotor mit Bindungsstelle für PU.1 nicht mehr aktivieren. Wir zeigen, dass der Leuzin-Zipper in der DNA-bindenden Domäne von C/EBPalpha mit der beta3/beta4-Region in der DNA-bindenden Domäne von PU.1 interagieren kann. Dadurch wird der Koaktivator von PU.1, c-jun, aus seiner Bindung mit PU.1 verdrängt. C/EBPalpha hemmt PU.1 nicht, indem es Korepressoren rekrutiert. Vielmehr vermindert C/EBPalpha die Expression von PU.1 in U-937-Zellen mit induzierbarem C/EBPalpha, indem es den autoregulatorischen Effekt PU.1 auf den PU.1-Promotor hemmt.
Ausserdem blockiert C/EBPalpha die durch PU.1 bedingte Entwicklung dendritischer Zellen aus CD34+ menschlichen Nabel blutzellen. Diese funktionelle Blockade von PU.1 durch C/EBPalpha könnte einer der Mechanismen sein, mit denen C/EBPalpha den durch PU.1 determinierten Weg der Zelldifferenzierung hemmt und sich Zellen unter dem Einfluss von C/EBPalpha zu Granulozyten entwickeln.Several transcription factors have been shown to play a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of both myeloid and lymphoid lineages while the transcription factor CCAAT/enhancer binding protein family member C/EBPalpha is essential for granulocytic development. We present here the first evidence that C/EBPalpha blocks the function of PU.1. PU.1 and C/EBPalpha interact physically and co-localize in myeloid cells. As a consequence of this interaction C/EBPalpha can inhibit the function of PU.1 to activate a minimal promoter containing only PU.1 DNA binding sites. We further demonstrate that the leucine zipper in the DNA binding domain of C/EBPalpha interacts with the beta3/beta4 region in the DNA binding domain of PU.1, and as a result displaces the PU.1 co-activator c-Jun. Finally, C/EBPalpha blocks PU.1 induced dendritic cell development from CD34+ human cord blood cells. The functional blocking of PU.1 by C/EBPalpha could be the mechanism by which C/EBPalpha inhibits the cell fates specified by PU.1, and directs cell development to the granulocytic lineage
Differentiation of the mononuclear phagocyte system during mouse embryogenesis:the role of transcription factor PU.1
No full textDuring mouse embryogenesis, macrophage-like cells arise first in the yolk sac and are produced subsequently in the liver. The onset of liver hematopoiesis is associated with the transition from primitive to definitive erythrocyte production. This report addresses the hypothesis that a similar transition in phenotype occurs in myelopoiesis. We have used whole mount in situ hybridization to detect macrophage-specific genes expressed during mouse development. The mouse c-fms mRNA, encoding the receptor for macrophage colony-stimulating factor (CSF-1), was expressed on phagocytic cells in the yolk sac and throughout the embryo before the onset of liver hematopoiesis. Similar cells were detected using the mannose receptor, the complement receptor (CR3), or the Microphthalmia transcription factor (MITF) as mRNA markers. By contrast, other markers including the F4/80 antigen, the macrophage scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the secretory product lysozyme appeared later in development and appeared restricted to only a subset of c-fms-positive cells. Two-color immunolabeling on disaggregated cells confirmed that CR3 and c-fms proteins are expressed on the same cells. Among the genes appearing later in development was the macrophage-restricted transcription factor, PU.1, which has been shown to be required for normal adult myelopoiesis. Mice with null mutations in PU.1 had normal numbers of c-fms-positive phagocytes at 11.5dpc. PU.1(-/-) embryonic stem cells were able to give rise to macrophage-like cells after cultivation in vitro. The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and the data of annual variation range of seawater temperature along the global coastline related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry (2019). Thermal effects on flow and salinity distribution in coastal confined aquifers. Submitted to Geophysical Research Letters
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and numerical simulation results related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry, Thermal effects on flow and salinity distribution in coastal confined aquifers, Submitted to Geophysical Research Letters
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and the data of annual variation range of seawater temperature along the global coastline related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry (2019). Thermal effects on flow and salinity distribution in coastal confined aquifers. Submitted to Geophysical Research Letters
Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and numerical simulation results related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry, Thermal effects on flow and salinity distribution in coastal confined aquifers, Submitted to Geophysical Research Letters
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and numerical simulation results related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry, Thermal effects on flow and salinity distribution in coastal confined aquifers, Submitted to Geophysical Research Letters
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data, the data of groundwater and seawater temperature along the global coastline and input files for the model used in the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry (2020). Thermal effects on flow and salinity distribution in coastal confined aquifers
Data for: Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and numerical simulation results related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry, Thermal effects on flow and salinity distribution in coastal confined aquifers, Submitted to Geophysical Research Letters
Thermal effects on flow and salinity distribution in coastal confined aquifers
No full textThis data set contains experimental data and numerical simulation results related to the paper - Li Pu, Pei Xin, Thuy T. M. Nguyen, Xiayang Yu, Ling Li, D. A. Barry, Thermal effects on flow and salinity distribution in coastal confined aquifers, Submitted to Geophysical Research Letters
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