Publications by authors named "Valérie Borel"

17 Publications

  • Page 1 of 1

Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD.

Mol Cell 2021 02 16;81(4):767-783.e11. Epub 2020 Dec 16.

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Artios Pharma Ltd., Meditrina, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address:

Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD cancers.
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http://dx.doi.org/10.1016/j.molcel.2020.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895907PMC
February 2021

TRF2-independent chromosome end protection during pluripotency.

Nature 2021 01 25;589(7840):103-109. Epub 2020 Nov 25.

The Francis Crick Institute, London, UK.

Mammalian telomeres protect chromosome ends from aberrant DNA repair. TRF2, a component of the telomere-specific shelterin protein complex, facilitates end protection through sequestration of the terminal telomere repeat sequence within a lariat T-loop structure. Deleting TRF2 (also known as TERF2) in somatic cells abolishes T-loop formation, which coincides with telomere deprotection, chromosome end-to-end fusions and inviability. Here we establish that, by contrast, TRF2 is largely dispensable for telomere protection in mouse pluripotent embryonic stem (ES) and epiblast stem cells. ES cell telomeres devoid of TRF2 instead activate an attenuated telomeric DNA damage response that lacks accompanying telomere fusions, and propagate for multiple generations. The induction of telomere dysfunction in ES cells, consistent with somatic deletion of Trf2 (also known as Terf2), occurs only following the removal of the entire shelterin complex. Consistent with TRF2 being largely dispensable for telomere protection specifically during early embryonic development, cells exiting pluripotency rapidly switch to TRF2-dependent end protection. In addition, Trf2-null embryos arrest before implantation, with evidence of strong DNA damage response signalling and apoptosis specifically in the non-pluripotent compartment. Finally, we show that ES cells form T-loops independently of TRF2, which reveals why TRF2 is dispensable for end protection during pluripotency. Collectively, these data establish that telomere protection is solved by distinct mechanisms in pluripotent and somatic tissues.
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http://dx.doi.org/10.1038/s41586-020-2960-yDOI Listing
January 2021

Synthetic Lethality between DNA Polymerase Epsilon and RTEL1 in Metazoan DNA Replication.

Cell Rep 2020 05;31(8):107675

The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK. Electronic address:

Genome stability requires coordination of DNA replication origin activation and replication fork progression. RTEL1 is a regulator of homologous recombination (HR) implicated in meiotic cross-over control and DNA repair in C. elegans. Through a genome-wide synthetic lethal screen, we uncovered an essential genetic interaction between RTEL1 and DNA polymerase (Pol) epsilon. Loss of POLE4, an accessory subunit of Pol epsilon, has no overt phenotype in worms. In contrast, the combined loss of POLE-4 and RTEL-1 results in embryonic lethality, accumulation of HR intermediates, genome instability, and cessation of DNA replication. Similarly, loss of Rtel1 in Pole4 mouse cells inhibits cellular proliferation, which is associated with persistent HR intermediates and incomplete DNA replication. We propose that RTEL1 facilitates genome-wide fork progression through its ability to metabolize DNA secondary structures that form during DNA replication. Loss of this function becomes incompatible with cell survival under conditions of reduced origin activation, such as Pol epsilon hypomorphy.
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http://dx.doi.org/10.1016/j.celrep.2020.107675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262601PMC
May 2020

CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle.

Nature 2019 11 13;575(7783):523-527. Epub 2019 Nov 13.

The Francis Crick Institute, London, UK.

The protection of telomere ends by the shelterin complex prevents DNA damage signalling and promiscuous repair at chromosome ends. Evidence suggests that the 3' single-stranded telomere end can assemble into a lasso-like t-loop configuration, which has been proposed to safeguard chromosome ends from being recognized as DNA double-strand breaks. Mechanisms must also exist to transiently disassemble t-loops to allow accurate telomere replication and to permit telomerase access to the 3' end to solve the end-replication problem. However, the regulation and physiological importance of t-loops in the protection of telomere ends remains unknown. Here we identify a CDK phosphorylation site in the shelterin subunit at Ser365 of TRF2, whose dephosphorylation in S phase by the PP6R3 phosphatase provides a narrow window during which the RTEL1 helicase can transiently access and unwind t-loops to facilitate telomere replication. Re-phosphorylation of TRF2 at Ser365 outside of S phase is required to release RTEL1 from telomeres, which not only protects t-loops from promiscuous unwinding and inappropriate activation of ATM, but also counteracts replication conflicts at DNA secondary structures that arise within telomeres and across the genome. Hence, a phospho-switch in TRF2 coordinates the assembly and disassembly of t-loops during the cell cycle, which protects telomeres from replication stress and an unscheduled DNA damage response.
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http://dx.doi.org/10.1038/s41586-019-1744-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874499PMC
November 2019

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

Am J Hum Genet 2018 12 29;103(6):1038-1044. Epub 2018 Nov 29.

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. Electronic address:

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.
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http://dx.doi.org/10.1016/j.ajhg.2018.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288413PMC
December 2018

Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis.

Mol Cell 2018 05 10;70(4):707-721.e7. Epub 2018 May 10.

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

DNA polymerase ε (POLE) is a four-subunit complex and the major leading strand polymerase in eukaryotes. Budding yeast orthologs of POLE3 and POLE4 promote Polε processivity in vitro but are dispensable for viability in vivo. Here, we report that POLE4 deficiency in mice destabilizes the entire Polε complex, leading to embryonic lethality in inbred strains and extensive developmental abnormalities, leukopenia, and tumor predisposition in outbred strains. Comparable phenotypes of growth retardation and immunodeficiency are also observed in human patients harboring destabilizing mutations in POLE1. In both Pole4 mouse and POLE1 mutant human cells, Polε hypomorphy is associated with replication stress and p53 activation, which we attribute to inefficient replication origin firing. Strikingly, removing p53 is sufficient to rescue embryonic lethality and all developmental abnormalities in Pole4 null mice. However, Pole4p53 mice exhibit accelerated tumorigenesis, revealing an important role for controlled CMG and origin activation in normal development and tumor prevention.
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http://dx.doi.org/10.1016/j.molcel.2018.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972231PMC
May 2018

Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe.

Cell 2018 01 28;172(3):439-453.e14. Epub 2017 Dec 28.

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1 cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells. In this context, we establish that telomerase binding to reversed replication forks inhibits telomere replication, which can be mimicked by preventing replication fork restart through depletion of RECQ1 or PARG. Our results lead us to propose that telomerase inappropriately binds to and inhibits restart of reversed replication forks within telomeres, which compromises replication and leads to critically short telomeres.
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http://dx.doi.org/10.1016/j.cell.2017.11.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786504PMC
January 2018

FANCJ suppresses microsatellite instability and lymphomagenesis independent of the Fanconi anemia pathway.

Genes Dev 2015 Dec 4;29(24):2532-46. Epub 2015 Dec 4.

DNA Damage Response Laboratory, Clare Hall Laboratories, The Francis Crick Institute, South Mimms EN6 3LD, United Kingdom;

Microsatellites are short tandem repeat sequences that are highly prone to expansion/contraction due to their propensity to form non-B-form DNA structures, which hinder DNA polymerases and provoke template slippage. Although error correction by mismatch repair plays a key role in preventing microsatellite instability (MSI), which is a hallmark of Lynch syndrome, activities must also exist that unwind secondary structures to facilitate replication fidelity. Here, we report that Fancj helicase-deficient mice, while phenotypically resembling Fanconi anemia (FA), are also hypersensitive to replication inhibitors and predisposed to lymphoma. Whereas metabolism of G4-DNA structures is largely unaffected in Fancj(-/-) mice, high levels of spontaneous MSI occur, which is exacerbated by replication inhibition. In contrast, MSI is not observed in Fancd2(-/-) mice but is prevalent in human FA-J patients. Together, these data implicate FANCJ as a key factor required to counteract MSI, which is functionally distinct from its role in the FA pathway.
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http://dx.doi.org/10.1101/gad.272740.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699383PMC
December 2015

BOD1L Is Required to Suppress Deleterious Resection of Stressed Replication Forks.

Mol Cell 2015 Aug 9;59(3):462-77. Epub 2015 Jul 9.

School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK. Electronic address:

Recognition and repair of damaged replication forks are essential to maintain genome stability and are coordinated by the combined action of the Fanconi anemia and homologous recombination pathways. These pathways are vital to protect stalled replication forks from uncontrolled nucleolytic activity, which otherwise causes irreparable genomic damage. Here, we identify BOD1L as a component of this fork protection pathway, which safeguards genome stability after replication stress. Loss of BOD1L confers exquisite cellular sensitivity to replication stress and uncontrolled resection of damaged replication forks, due to a failure to stabilize RAD51 at these forks. Blocking DNA2-dependent resection, or downregulation of the helicases BLM and FBH1, suppresses both catastrophic fork processing and the accumulation of chromosomal damage in BOD1L-deficient cells. Thus, our work implicates BOD1L as a critical regulator of genome integrity that restrains nucleolytic degradation of damaged replication forks.
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http://dx.doi.org/10.1016/j.molcel.2015.06.007DOI Listing
August 2015

HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis.

Nature 2013 Oct 4;502(7471):381-4. Epub 2013 Sep 4.

DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK.

Repair of interstrand crosslinks (ICLs) requires the coordinated action of the intra-S-phase checkpoint and the Fanconi anaemia pathway, which promote ICL incision, translesion synthesis and homologous recombination (reviewed in refs 1, 2). Previous studies have implicated the 3'-5' superfamily 2 helicase HELQ in ICL repair in Drosophila melanogaster (MUS301 (ref. 3)) and Caenorhabditis elegans (HELQ-1 (ref. 4)). Although in vitro analysis suggests that HELQ preferentially unwinds synthetic replication fork substrates with 3' single-stranded DNA overhangs and also disrupts protein-DNA interactions while translocating along DNA, little is known regarding its functions in mammalian organisms. Here we report that HELQ helicase-deficient mice exhibit subfertility, germ cell attrition, ICL sensitivity and tumour predisposition, with Helq heterozygous mice exhibiting a similar, albeit less severe, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks. Thus, our results reveal a critical role for HELQ in replication-coupled DNA repair, germ cell maintenance and tumour suppression in mammals.
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http://dx.doi.org/10.1038/nature12565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836231PMC
October 2013

RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection.

Mol Cell 2013 Mar 17;49(5):858-71. Epub 2013 Jan 17.

DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, London, UK.

The appropriate execution of DNA double-strand break (DSB) repair is critical for genome stability and tumor avoidance. 53BP1 and BRCA1 directly influence DSB repair pathway choice by regulating 5' end resection, but how this is achieved remains uncertain. Here we report that Rif1(-/-) mice are severely compromised for 53BP1-dependent class switch recombination (CSR) and fusion of dysfunctional telomeres. The inappropriate accumulation of RIF1 at DSBs in S phase is antagonized by BRCA1, and deletion of Rif1 suppresses toxic nonhomologous end joining (NHEJ) induced by PARP inhibition in Brca1-deficient cells. Mechanistically, RIF1 is recruited to DSBs via the N-terminal phospho-SQ/TQ domain of 53BP1, and DSBs generated by ionizing radiation or during CSR are hyperresected in the absence of RIF1. Thus, RIF1 and 53BP1 cooperate to block DSB resection to promote NHEJ in G1, which is antagonized by BRCA1 in S phase to ensure a switch of DSB repair mode to homologous recombination.
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http://dx.doi.org/10.1016/j.molcel.2013.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594748PMC
March 2013

MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism.

Science 2012 Jul 7;337(6091):243-5. Epub 2012 Jun 7.

DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK.

The function of many DNA metabolism proteins depends on their ability to coordinate an iron-sulfur (Fe-S) cluster. Biogenesis of Fe-S proteins is a multistep process that takes place in mitochondria and the cytoplasm, but how it is linked to nuclear Fe-S proteins is not known. Here, we demonstrate that MMS19 forms a complex with the cytoplasmic Fe-S assembly (CIA) proteins CIAO1, IOP1, and MIP18. Cytoplasmic MMS19 also binds to multiple nuclear Fe-S proteins involved in DNA metabolism. In the absence of MMS19, a failure to transfer Fe-S clusters to target proteins is associated with Fe-S protein instability and preimplantation death of mice in which Mms19 has been knocked out. We propose that MMS19 functions as a platform to facilitate Fe-S cluster transfer to proteins critical for DNA replication and repair.
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http://dx.doi.org/10.1126/science.1219664DOI Listing
July 2012

Ontogeny of aquaporins in human fetal membranes.

Biol Reprod 2012 Feb 29;86(2):48. Epub 2012 Feb 29.

Laboratoire de Biochimie Médicale, Génétique Reproduction et Développement, Clermont-Université Institut National de la Santé et de la Recherche Médicale Unité, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France.

It has been proposed that four members of the aquaporin family (AQPs 1, 3, 8, and 9) are involved in the control of amniotic fluid (AF) homeostasis, as illustrated by their differential expression patterns in normal and pathological human term fetal membranes. However, there are no data available to date on their ontogeny throughout pregnancy. Our objective was to determine spatiotemporal expression profiles of the mRNA and proteins of all 13 members of this transmembrane channel family. For this purpose, we used healthy fetal membranes from the first, second, and third trimesters of pregnancy. Total mRNA and proteins were extracted from total membranes and from separated amnion and chorion. Quantitative PCR, Western blot, and immunohistochemistry experiments were carried out to determine the presence of AQPs and to quantify their spatiotemporal expression patterns throughout pregnancy. The WISH cell line was tested to propose a cellular model for the role of AQPs in the amnion compartment. AQP11 expression was established in amniotic membranes at term. Aquaporins 1, 3, 8, 9, and 11 mRNA and proteins were present in amnion and chorion throughout human gestation. Each AQP has a time-specific expression pattern, with AQP1 presenting the highest variation in terms of mRNA and protein levels. The WISH cell line also expressed the same five AQPs. Taken together, these results indicate that AQPs are expressed and potentially involved in the regulation of AF homeostasis throughout pregnancy. This also clearly supports the hypothesis that abnormal expression could occur at any time during pregnancy, ultimately leading to obstetrical pathologies such as polyhydramnios or oligohydramnios.
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http://dx.doi.org/10.1095/biolreprod.111.095448DOI Listing
February 2012

Retinoids regulate human amniotic tissue-type plasminogen activator gene by a two-step mechanism.

J Cell Mol Med 2010 Jun 16;14(6B):1793-805. Epub 2009 Jun 16.

Génétique Reproduction et Développement (GReD), UMR CNRS 6247, Clermont Université, INSERM U931, Faculté de Médecine, Clermont-Ferrand, France.

The collagenolytic effects of the tissue-type plasminogen activator (t-PA) leading to extracellular matrix degradation are clearly involved in the physiopathology of human foetal membranes rupture. Nevertheless, the regulation of t-PA gene expression in extraembryonic developmental contexts remains unknown. The aim of our study is to propose the retinoic acids (RAs) as molecular regulators of t-PA expression in foetal membranes. RA induced t-PA mRNA and proteins in a time-dependent manner in amniotic membrane explants and Wistar Institute Susan Hayflick (WISH) cells. Furthermore, the use of cycloheximide revealed a two-step regulation of t-PA gene. Gene reporter assays confirmed that the RA-induced t-PA gene expression occurred through interactions of retinoid receptors (RARs and RXRs) with a DR5 response element located at -7 kb from the transcription site. Site-directed mutagenesis of this region of the t-PA promoter showed that SP1 factor was also retinoid-mediated induction, and immunoprecipitation assays revealed that SP1 and RAR/RXR interacted physically. Chromatin immunoprecipitation demonstrated that interactions between RARs, RXRs and t-PA promoter were time dependent: RAR-alpha/RXR-alpha bound DR5 motif before and up to 12 hrs of RA exposure, and RAR-beta/RXR-alpha bound DR5 response element after 12 hrs of RA treatment. Finally, experiments using shRNA and RAR-beta-specific antagonist revealed that reducing RAR-beta induction decreased t-PA induction. Altogether, our results established that the RA-mediated regulation of t-PA in human foetal membranes occurred through two steps, with a major role played by RAR-beta.
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http://dx.doi.org/10.1111/j.1582-4934.2009.00802.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829039PMC
June 2010

Placental implications of peroxisome proliferator-activated receptors in gestation and parturition.

PPAR Res 2008 ;2008:758562

Université d'Auvergne, JE 2447, ARDEMO, 63000 Clermont-Ferrand, France.

The placenta is a transitory structure indispensable for the proper development of the embryo and fetus during mammalian gestation. Like other members of the nuclear receptor family, the peroxisome proliferator-activated receptors (PPARs) are known to be involved in the physiological and pathological events occurring during the placentation. This placental involvement has been recently reviewed focusing on the early stages of placental development (implantation and invasion, etc.), mouse PPARs knockout phenotypes, and cytotrophoblast physiology. In this review, we describe the placental involvement of PPARs (e.g., fat transport and metabolism, etc.) during the late stages of gestation and in the amniotic membranes, highlighting their roles in the inflammation process (e.g., chorioamnionitis), metabolic disorders (e.g., diabetes), and parturition.
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http://dx.doi.org/10.1155/2008/758562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234353PMC
July 2011

Molecular and metabolic retinoid pathways in human amniotic membranes.

Biochem Biophys Res Commun 2006 Aug 12;346(4):1207-16. Epub 2006 Jun 12.

Université d'Auvergne, JE 2447, ARDEMO, F-63000 Clermont-Ferrand, France.

Vitamin A (retinol) and its active derivatives (the retinoids) are essential for the growth and development of the mammalian fetus and placenta. The amniotic membranes are extra-embryonic structures that are indispensable for normal gestation in mammals. Although placental involvement of retinoids is clearly established, little is known about the roles of retinoids for the associated amniotic membranes. The aim of this study was to define the metabolic and molecular pathways of retinoic signaling in human fetal membranes. The expression of retinoid receptors (RARalpha, beta and RXRalpha, beta) was established at transcript and protein levels. Enzymes involved in retinoic acid generation were also detected. The enzymatic generation of functional retinoids was confirmed using specific inhibitors of retinol metabolism. Finally, the functionality of retinoid pathways was demonstrated by inducing established retinoid target gene expression. Our results clearly demonstrated that the molecular and metabolic actors of retinoic signaling pathways are functional in human fetal membranes.
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http://dx.doi.org/10.1016/j.bbrc.2006.06.024DOI Listing
August 2006

Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1.

Biochem Biophys Res Commun 2006 May 20;343(3):745-53. Epub 2006 Mar 20.

INSERM U.384, Laboratoire de Biochimie, Faculté de Médecine, F-63000 Clermont-Ferrand, France.

Pregnancy-specific glycoproteins (PSGs) are major placental proteins thought to be essential for the maintenance of gestation. Little is known about the regulation of expression of the 11 genes encoding these proteins. It was previously demonstrated that Krüppel-like factor 6 (KLF6) and specific-protein 1 (Sp1) bind to conserved sequence within the PSG-5 gene promoter. Informatics analysis revealed the presence of one potential binding site for Krüppel-like factor 4 (KLF4), in the PSG-5 promoter, suggesting a potential transcriptional regulator role for KLF4. Using gene promoter-reporter transfections and X-ChIP assays, we demonstrated that KLF4 is an activator of the PSG-5 promoter by binding to a KLF consensus like binding which includes the Core Promoter Element region (-147/-140). Furthermore, we used previous data showing the binding of Sp1 transcription factor to a GT-box (-443/-437) and co-transfection assays with KLF4 and Sp1 to demonstrate the strong synergic activity of these two factors on the PSG-5 promoter.
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http://dx.doi.org/10.1016/j.bbrc.2006.03.032DOI Listing
May 2006