The Ets transcription factor PU.1 is essential for inducing the differentiation of monocytes, macrophages, and B cells in fetal liver and adult bone marrow. PU.1 controls hematopoietic differentiation through physical interactions with other transcription factors, such as C/EBPα and the AP-1 family member c-Jun. We found that PU.1 recruits c-Jun to promoters without the AP-1 binding sites. To address the functional importance of this interaction, we generated PU.1 point mutants that do not bind c-Jun while maintaining normal DNA binding affinity. These mutants lost the ability to transactivate a target reporter that requires a physical PU.1-c-Jun interaction, and did not induce monocyte/macrophage differentiation of PU.1-deficient cells. Knock-in mice carrying these point mutations displayed an almost complete block in hematopoiesis and perinatal lethality. While the PU.1 mutants were expressed in hematopoietic stem and early progenitor cells, myeloid differentiation was severely blocked, leading to an almost complete loss of mature hematopoietic cells. Differentiation into mature macrophages could be restored by expressing PU.1 mutant fused to c-Jun, demonstrating that a physical PU.1-c-Jun interaction is crucial for the transactivation of PU.1 target genes required for myeloid commitment and normal PU.1 function in vivo during macrophage differentiation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9474506 | PMC |
| http://dx.doi.org/10.1038/s42003-022-03888-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The interaction of bacteria and harmonine in harlequin ladybird confers an interspecies competitive edge.
Proc Natl Acad Sci U S A
January 2025
Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The harlequin ladybird, , is a predatory beetle used globally to control pests such as aphids and scale insects. Originating from East Asia, this species has become highly invasive since its introduction in the late 19th century to Europe and North America, posing a threat to local biodiversity. Intraguild predation is hypothesized to drive the success of this invasive species, but the underlying mechanisms remain unknown.
View Article and Find Full Text PDFChromatin enables precise and scalable gene regulation with factors of limited specificity.
Proc Natl Acad Sci U S A
January 2025
Institute of Science and Technology Austria, AT-3400 Klosterneuburg, Austria.
Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs).
View Article and Find Full Text PDFTetrameric PilZ protein stabilizes stator ring in complex flagellar motor and is required for motility in .
Proc Natl Acad Sci U S A
January 2025
Chinese Academy of Sciences Key Laboratory of Tropical Marine Bio Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, Guangdong Provincial Observation and Research Station for Coastal Upwelling Ecosystem, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 511458, China.
Rotation of the bacterial flagellum, the first identified biological rotary machine, is driven by its stator units. Knowledge gained about the function of stator units has increasingly led to studies of rotary complexes in different cellular pathways. Here, we report that a tetrameric PilZ family protein, FlgX, is a structural component underneath the stator units in the flagellar motor of .
View Article and Find Full Text PDFMoisture-driven carbonation kinetics for ultrafast CO mineralization.
Proc Natl Acad Sci U S A
January 2025
Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, China.
CO mineralization, a process where CO reacts with minerals to form stable carbonates, presents a sustainable approach for CO sequestration and mitigation of global warming. While the crucial role of water in regulating CO mineralization efficiency is widely acknowledged, a comprehensive understanding of the underlying mechanisms remains elusive. This study employs a combined experimental and atomistic simulation approach to elucidate the intricate mechanisms governing moisture-driven carbonation kinetics of calcium-bearing minerals.
View Article and Find Full Text PDFProtein dynamics underlies strong temperature dependence of heat receptors.
Proc Natl Acad Sci U S A
January 2025
Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214.
Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!