Runx3-mediated Transcriptional Program in Cytotoxic Lymphocytes

Lotem, Joseph; Levanon, Ditsa; Negreanu, Varda; Leshkowitz, Dena; Friedlander, Gilgi; Groner, Yoram
November 2013
PLoS ONE;Nov2013, Vol. 8 Issue 11, p1
Academic Journal
The transcription factor Runx3 is highly expressed in CD8+ T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still missing. Using Runx3-ChIP-seq and transcriptome analysis of wild type vs. Runx3-/- primary cells we have now identified Runx3-regulated genes in the two cell types at both resting and IL-2-activated states. Runx3-bound genomic regions in both cell types were distantly located relative to gene transcription start sites and were enriched for RUNX and ETS motifs. Bound genomic regions significantly overlapped T-bet and p300-bound enhancer regions in Runx3-expressing Th1 helper cells. Compared to resting cells, IL-2-activated CD8+ T and NK cells contain three times more Runx3-regulated genes that are common to both cell types. Functional annotation of shared CD8+ T and NK Runx3-regulated genes revealed enrichment for immune-associated terms including lymphocyte activation, proliferation, cytotoxicity, migration and cytokine production, highlighting the role of Runx3 in CD8+ T and NK activated cells.


Related Articles

  • PLZF controls the expression of a limited number of genes essential for NKT cell function. Gleimer, Michael; von Boehmer, Harald; Kreslavsky^1,2, Taras // Frontiers in Immunology;Dec2012, Vol. 3, p1 

    Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is...

  • Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways. Dybkaer, Karen; Iqbal, Javeed; Guimei Zhou; Huimin Geng; Li Xiao; Schmitz, Alexander; d'Amore, Francesco; Chan, Wing C // BMC Genomics;2007, Vol. 8, p230 

    Background: Human natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways...

  • Let-7 replacement therapy: applicability in cancer. Barh, Debmalya // Cancer Therapy;2008, Vol. 6 Issue 2, p969 

    The endogenous non-coding pool of microRNAs (miRs) has been found to regulate several biological processes by transcriptionally or post-transcriptionally regulating gene expression. It has also been reported that miRs are differentionally expressed and deregulated in several patho-physiological...

  • SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin. Brandt, Dominique T.; Baarlink, Christian; Kitzing, Thomas M.; Kremmer, Elisabeth; Ivaska, Johanna; Nollau, Peter; Grosse, Robert // Nature Cell Biology;May2009, Vol. 11 Issue 5, p557 

    Gene expression reprogramming governs cellular processes such as proliferation, differentiation and cell migration through the complex and tightly regulated control of transcriptional cofactors that exist in multiprotein complexes. Here we describe SCAI (suppressor of cancer cell invasion), a...

  • Molecular determinants of the profibrogenic effects of endothelin-1 in pancreatic stellate cells. Jonitz, Anika; Fitzner, Brit; Jaster, Robert; Arai, Masahiro // World Journal of Gastroenterology;9/7/2009, Vol. 15 Issue 33, p4143 

    AIM: To gain molecular insights into the expression and functions of endothelin-1 (ET-1) in pancreatic stellate cells (PSC). METHODS: PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-1 or other extra-cellular mediators. Cell proliferation was assessed by measuring...

  • P63 regulates tubular formation via epithelial-to-mesenchymal transition. Zhang, Y; Yan, W; Chen, X // Oncogene;3/20/2014, Vol. 33 Issue 12, p1548 

    P63, a p53 family member, is expressed as TA and ΔN isoforms. Interestingly, both TAp63 and ΔNp63 are transcription factors, and regulate both common and distinct sets of target genes. p63 is required for survival of some epithelial cell lineages, and lack of p63 leads to loss of...

  • Regulation of the p27Kip1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. le Sage, Carlos; Nagel, Remco; Egan, David A.; Schrier, Mariette; Mesman, Elly; Mangiola, Annunziato; Anile, Corrado; Maira, Giulio; Mercatelli, Neri; Ciafrè, Silvia Anna; Farace, Maria Giulia; Agami, Reuven // EMBO Journal;8/8/2007, Vol. 26 Issue 15, p3699 

    MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein coding genes. Patterns of misexpression of miRNAs in cancer suggest key functions of miRNAs in tumorigenesis. However, current bioinformatics tools do not entirely support the identification and characterization of the mode...

  • FoxM1, a critical regulator of oxidative stress during oncogenesis. Park, Hyun Jung; Carr, Janai R.; Zebin Wang; Nogueira, Veronique; Hay, Nissim; Tyner, Angela L.; Lau, Lester F.; Costa, Robert H.; Raychaudhuri, Pradip // EMBO Journal;10/7/2009, Vol. 28 Issue 19, p2908 

    The transcription factor FoxM1 is over-expressed in most human malignancies. Although it is evident that FoxM1 has critical functions in tumour development and progression, the mechanisms by which FoxM1 participates in those processes are not understood. Here, we describe an essential role of...

  • microRNA-200a Inhibits Cell Proliferation by Targeting Mitochondrial Transcription Factor A in Breast Cancer. Yao, Jia; Zhou, Enxiang; Wang, Yichun; Xu, Feng; Zhang, Danhua; Zhong, Dewu // DNA & Cell Biology;May2014, Vol. 33 Issue 5, p291 

    microRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-200a expression levels were decreased while mitochondrial transcription factor A...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics