Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition
Emmanuelle Deniaud,Joël Baguet,Roxane Chalard,Roxane Chalard,Bariza Blanquier,Lilia Brinza,Julien Meunier,Julien Meunier,Marie-Cécile Michallet,Aurélie Laugraud,Claudette Ah-Soon,Anne Wierinckx,Marc Castellazzi,Joël Lachuer,Christian Gautier,Jacqueline Marvel,Yann Leverrier +16 more
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TLDR
It is shown that the binding to DNA of overexpressed Sp1 induces an inhibition of cell cycle progression that precedes apoptosis and a transcriptional response targeting genes containing Sp1 binding sites in their promoter or not suggesting both direct Sp1-driven transcription and indirect mechanisms.Abstract:
BACKGROUND: The ubiquitous transcription factor Sp1 regulates the expression of a vast number of genes involved in many cellular functions ranging from differentiation to proliferation and apoptosis. Sp1 expression levels show a dramatic increase during transformation and this could play a critical role for tumour development or maintenance. Although Sp1 deregulation might be beneficial for tumour cells, its overexpression induces apoptosis of untransformed cells. Here we further characterised the functional and transcriptional responses of untransformed cells following Sp1 overexpression. METHODOLOGY AND PRINCIPAL FINDINGS: We made use of wild-type and DNA-binding-deficient Sp1 to demonstrate that the induction of apoptosis by Sp1 is dependent on its capacity to bind DNA. Genome-wide expression profiling identified genes involved in cancer, cell death and cell cycle as being enriched among differentially expressed genes following Sp1 overexpression. In silico search to determine the presence of Sp1 binding sites in the promoter region of modulated genes was conducted. Genes that contained Sp1 binding sites in their promoters were enriched among down-regulated genes. The endogenous sp1 gene is one of the most down-regulated suggesting a negative feedback loop induced by overexpressed Sp1. In contrast, genes containing Sp1 binding sites in their promoters were not enriched among up-regulated genes. These results suggest that the transcriptional response involves both direct Sp1-driven transcription and indirect mechanisms. Finally, we show that Sp1 overexpression led to a modified expression of G1/S transition regulatory genes such as the down-regulation of cyclin D2 and the up-regulation of cyclin G2 and cdkn2c/p18 expression. The biological significance of these modifications was confirmed by showing that the cells accumulated in the G1 phase of the cell cycle before the onset of apoptosis. CONCLUSION: This study shows that the binding to DNA of overexpressed Sp1 induces an inhibition of cell cycle progression that precedes apoptosis and a transcriptional response targeting genes containing Sp1 binding sites in their promoter or not suggesting both direct Sp1-driven transcription and indirect mechanisms.read more
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Down‐regulation of single immunoglobulin interleukin‐1R‐related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation
Chikara Kadota,Shunji Ishihara,Monowar Aziz,Mohammad Azharul Karim Rumi,Naoki Oshima,Yoshiyuki Mishima,Ichiro Moriyama,Takafumi Yuki,Yuji Amano,Yoshikazu Kinoshita +9 more
TL;DR: It is found that SIGIRR is expressed in IECs and serves as a negative regulator to maintain gut innate immunity, which is down‐regulated during inflammation by inhibition of an SP1‐mediated pathway.
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Research Resource: Progesterone Receptor Targetome Underlying Mammary Gland Branching Morphogenesis
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Dose-dependent activation of putative oncogene SBSN by BORIS.
Daria A. Gaykalova,Rajita Vatapalli,Chad A. Glazer,Sheetal Bhan,Chunbo Shao,David Sidransky,David Sidransky,Patrick K. Ha,Patrick K. Ha,Joseph A. Califano,Joseph A. Califano +10 more
TL;DR: It is established that SBSN is a novel non-CTA target of BORIS epigenetic regulation, and it is demonstrated that relative BORis dosage is critical for SBSn activation.
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Harnessing the potential of plant transcription factors in developing climate resilient crops to improve global food security: Current and future perspectives
Rahil Shahzad,Shakra Jamil,Shakeel Ahmad,Amina Nisar,Zarmaha Amina,Shazmina Saleem,Muhammad Zaffar Iqbal,Rana Muhammad Atif,Xiukang Wang +8 more
TL;DR: The role of different stress-responsive plant transcriptional factors with respect to biotic and abiotic stresses is summarized in this paper, where challenges and future opportunities linked with TFs for developing climate-resilient crops are also elaborated.
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HIF-1α depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs.
TL;DR: The data reveals that knockdown of HIF-1α results in a significant increase in cells in the G1 phase of the cell cycle, and suggests that p21 is induced via, at least in part, p53-independent but SP1-dependent mechanisms.
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