Enforcing the pause: Transcription factor Sp3 limits productive elongation by RNA polymerase II

Valín, Álvaro; Gill, Grace

doi:10.4161/cc.24992

Cited by 3 publications

(3 citation statements)

References 87 publications

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“…However, we clearly show that, in chondrocytes, Sp3 acts as a potent repressor of COL1A1 expression. Such a dual function of Sp3, sometimes depending on the cell type, has been already described (26,27).…”

Section: Figmentioning

confidence: 95%

Hypoxia inducible factor 1 alpha down‐regulates type i collagen through Sp3 transcription factor in human chondrocytes

et al. 2016

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Cartilage engineering is one challenging issue in regenerative medicine. Low oxygen tension or hypoxia inducible factor-1 (HIF-1a) gene therapy are promising strategies in the field of cartilage repair. Previously, we showed that hypoxia and its mediator HIF-1 regulate matrix genes expression (collagens and aggrecan). Here, we investigated the molecular mechanism involved in the regulation of type I collagen (COL1A1) by HIF-1 in human articular chondrocytes. We show that HIF-1a reduces COL1A1 transcription, through a distal promoter (22300 to 21816 bp upstream transcription initiation site), containing two GC boxes that bind Sp transcription factors (Sp1/Sp3). Sp1 acts as a positive regulator but is not induced by HIF-1. COL1A1 inhibition caused by HIF-1 implies only Sp3, which accumulates and competes Sp1 binding on COL1A1 promoter. Additionally, Sp3 ectopic expression inhibits COL1A1, while Sp3 knockdown counteracts the downregulation of COL1A1 induced by HIF-1. In conclusion, we established a new regulatory model of COL1A1 regulation by HIF-1, and bring out its relationship with Sp3 transcription factor. In a fundamental level, these findings give insights in the mechanisms controlling COL1A1 gene expression. This may be helpful to improve strategies to impair type I collagen expression during chondrocyte differentiation for cartilage engineering.

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Section: Figmentioning

confidence: 95%

Hypoxia inducible factor 1 alpha down‐regulates type i collagen through Sp3 transcription factor in human chondrocytes

et al. 2016

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“…Likewise, Robo3 up‐regulation was detected in embryonic fibroblast cultures from mice deficient for the ubiquitous transcription factor (TF) Sp3 (Stielow et al, ). Sp3 is associated with gene silencing via heterochromatin formation and inhibition of RNApol‐II effective transcription (Valin and Gill, ). Loosening of Robo3 constitutive repression could be induced by the TF Pax2, binding to RB and inhibiting its repression activity on Robo3 (Yuan et al, ).…”

Section: Robo3 Gene Expression Is Tightly Regulatedmentioning

confidence: 99%

The Robo3 receptor, a key player in the development, evolution, and function of commissural systems

Friocourt

Chédotal

2017

Developmental Neurobiology

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Roundabout receptors are known to mediate Slit-dependent repulsive signaling. However in vertebrates, mounting evidence suggest that Robo3 is an unconventional Robo receptor regarding both its expression and function. From its initial description, the Robo3 receptor has been tightly associated with the development of specific axons, called commissural, that connect both sides of the nervous system. Many studies using transgenic mouse models showed that Robo3 expression is mandatory for commissural axon guidance to the floor plate. Moreover, mutations in human ROBO3 are responsible for a rare neurological disease in which patients also display midline crossing defects. Robo3 was initially thought to counteract Slit/Robo repulsion. However, recent studies support an alternative model where Robo3 potentiates midline attraction. These studies support a complex, central and multifaceted role of Robo3 in controlling the development of commissural circuits. Furthermore, the analysis of Robo3 evolution in vertebrates points out the specificity of this receptor in the mammalian lineage, suggesting mechanistic and functional divergence of Robo3 in mammals compared to a more traditional function in other vertebrates. Here, we review the current knowledge about Robo3 function, from the regulation of its expression to signaling. We also present evidence for a high variability of Robo3 splice variants in vertebrates. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 876-890, 2017.

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“…However, in genes with multiple GC sequences, Sp3 can either activate or repress transcription ( Birnbaum et al, 1995 ; Dennig et al, 1996 ; Sjottem et al, 1996 ). The inhibitory function of Sp3 may require post-translational modifications and could involve interfering with higher order Sp1 complex formation or facilitating recruitment of other transcriptional repressors ( Valin and Gill, 2013 ; Stielow et al, 2010 ; Sapetschnig et al, 2002 ; Ross et al, 2002 ). Co-expressed in most cells, Sp1 and Sp3 appear to localize to distinct nuclear regions ( He et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Sp3 is essential for normal lung morphogenesis and cell cycle progression during mouse embryonic development

et al. 2023

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Members of the Sp family of transcription factors regulate gene expression via binding GC boxes within promoter regions. Unlike Sp1, which stimulates transcription, the closely related Sp3 can either repress or activate gene expression and is required for perinatal survival in mice. Here we use RNAseq and cellular phenotyping to show how Sp3 regulates murine fetal cell differentiation and proliferation. Homozygous Sp3−/- mice were smaller than WT and Sp+/- littermates, died soon after birth, and had abnormal lung morphogenesis. RNAseq of Sp3−/- fetal lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways, and myofibroblast/lipofibroblast differentiation. The lungs of Sp3−/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3−/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development.

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Enforcing the pause: Transcription factor Sp3 limits productive elongation by RNA polymerase II

Cited by 3 publications

References 87 publications

Hypoxia inducible factor 1 alpha down‐regulates type i collagen through Sp3 transcription factor in human chondrocytes

Hypoxia inducible factor 1 alpha down‐regulates type i collagen through Sp3 transcription factor in human chondrocytes

The Robo3 receptor, a key player in the development, evolution, and function of commissural systems

Sp3 is essential for normal lung morphogenesis and cell cycle progression during mouse embryonic development

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