In the thymus, several steps of proliferative expansion and selection coordinate the maturation of precursors into antigen-specific T cells. Here we identify the transcriptional repressor Gfi1 as an important regulator of this maturation process. Mice lacking Gfi1 show reduced thymic cellularity due to an increased cell death rate, lack of proliferation, and a differentiation block in the very early uncommitted CD4-/CD8-/c-Kit+ cytokine-dependent T cell progenitors that have not yet initiated VDJ recombination. In addition, Gfi1-deficient mice show increased major histocompatibility complex class I-restricted positive selection and develop significantly more CD8+ cells suggesting a requirement of Gfi1 for a correct CD4/CD8 lineage decision. Absence of Gfi1 correlates with high level expression of the genes for lung Krüppel-like factor (LKLF), inhibitor of DNA binding (Id)1 and Id2, suggesting the existence of new regulatory pathways in pre-T cell development and thymic selection in which Gfi1 acts upstream of LKLF as well as the E-proteins, which are negatively regulated by Id1 and Id2.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193890 | PMC |
| http://dx.doi.org/10.1084/jem.20021417 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Estrogen-related receptor gamma is a regulator of mitochondrial, autophagy, and immediate-early gene programs in spiny projection neurons: Relevance for transcriptional changes in Huntington disease.
Neurobiol Dis
January 2025
Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Southern Research, Birmingham, AL 35205, USA. Electronic address:
Mitochondrial dysfunction, transcriptional dysregulation, and protein aggregation are hallmarks of multiple neurodegenerative disorders, including Huntington's disease (HD). Strategies are needed to counteract these processes to restore neuronal health and function in HD. Recent evidence indicates that the transcription factor estrogen-related receptor gamma (ERRγ/Esrrg) is required for normal expression of mitochondrial, synaptic, and autophagy genes in neurons.
View Article and Find Full Text PDFThe GRAS transcription factor PtrPAT1 of functions in cold tolerance and modulates glycine betaine content by regulating the -like gene.
Hortic Res
January 2025
National Key Laboratory for Germplasm Innovation and Utilization of Horticultural Crops, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.
GRAS, termed after gibberellic acid insensitive (GAI), RGA (repressor of GA1), and SCR (scarecrow), is a plant-specific transcription factor crucial for plant development and stress response. However, understanding of the functions played by the GRAS members and their target genes in citrus is limited. In this study, we identified a cold stress-responsive GRAS gene from , designated as PtrPAT1, by yeast one-hybrid library screening using the promoter of , a betaine aldehyde dehydrogenase (BADH)-like gene.
View Article and Find Full Text PDFThe IclR-family transcriptional regulator XyrR controls flotation, motility, antibiotic production and virulence in sp. ATCC 39006.
Front Microbiol
January 2025
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
The opportunistic pathogen sp. ATCC 39006 (S39006) is a rod-shaped, motile, Gram-negative bacterium that produces a 𝛽-lactam antibiotic (a carbapenem) and a bioactive red-pigmented tripyrrole antibiotic, prodigiosin. It is also the only known enterobacterium that naturally produces intracellular gas vesicles (GVs), enabling cells to float in static water columns.
View Article and Find Full Text PDFPDE4 inhibitor rolipram represses hedgehog signaling via ubiquitin-mediated proteolysis of GLI transcription factors to regress breast cancer.
J Biol Chem
January 2025
Cell and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal, India, 741235. Electronic address:
Aberrant activation of the hedgehog (Hh) signaling pathway positively correlates with progression, invasion and metastasis of several cancers, including breast cancer. Although numerous inhibitors of the Hh signaling pathway are available, several oncogenic mutations of key components of the pathway, including Smoothened (Smo), have limited their capability to be developed as putative anti-cancer drugs. In this study, we have modulated the Hh signaling pathway in breast cancer using a specific FDA-approved phosphodiesterase 4 (PDE4) inhibitor rolipram.
View Article and Find Full Text PDFThe yeast checkpoint kinase Dun1p represses transcription of RNR genes independently of catalytic activity or Rad53p during respiratory growth.
J Biol Chem
January 2025
Department of Biological Sciences, St. John's University, Queens, New York, USA. Electronic address:
One of the key events in DNA damage response (DDR) is activation of checkpoint kinases leading to activation of ribonucleotide reductase (RNR) and increased synthesis of deoxyribonucleotide triphosphates (dNTPs), required for DNA repair. Among other mechanisms, the activation of dNTP synthesis is driven by derepression of genes encoding RNR subunits RNR2, RNR3, and RNR4, following checkpoint activation and checkpoint kinase Dun1p-mediated phosphorylation and inactivation of transcriptional repressor Crt1p. We report here that in the absence of genotoxic stress during respiratory growth on nonfermentable carbon source acetate, inactivation of checkpoint kinases results in significant growth defect and alters transcriptional regulation of RNR2-4 genes and genes encoding enzymes of the tricarboxylic acid (TCA) and glyoxylate cycles and gluconeogenesis.
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!