Transcriptional Activation of REST by Sp1 in Huntington's Disease Models

In Huntington's disease (HD), mutant huntingtin (mHtt) disrupts the normal transcriptional program of disease neurons by altering the function of several gene expression regulators such as Sp1. REST (Repressor Element-1 Silencing Transcription Factor), a key regulator of neuronal differentiation, is also aberrantly activated in HD by a mechanism that remains unclear. Here, we show that the level of REST mRNA is increased in HD mice and in NG108 cells differentiated into neuronal-like cells and expressing a toxic mHtt fragment. Using luciferase reporter gene assay, we delimited the REST promoter regions essential for mHtt-mediated REST upregulation and found that they contain Sp factor binding sites. We provide evidence that Sp1 and Sp3 bind REST promoter and interplay to fine-tune REST transcription. In undifferentiated NG108 cells, Sp1 and Sp3 have antagonistic effect, Sp1 acting as an activator and Sp3 as a repressor. Upon neuronal differentiation, we show that the amount and ratio of Sp1/Sp3 proteins decline, as does REST expression, and that the transcriptional role of Sp3 shifts toward a weak activator. Therefore, our results provide new molecular information to the transcriptional regulation of REST during neuronal differentiation. Importantly, specific knockdown of Sp1 abolishes REST upregulation in NG108 neuronal-like cells expressing mHtt. Our data together with earlier reports suggest that mHtt triggers a pathogenic cascade involving Sp1 activation, which leads to REST upregulation and repression of neuronal genes

Fourier Transform Spectroscopy of the O2 Herzberg Bands: II. Band oscillator strengths and transition moments

From absorption spectra obtained at high resolution by coupling a Fourier transform spectrometer to a long-path multiple reflection cell the intensities of the O2 Herzberg bands (A3Σu+-X3Σg-, c1Σu-, A′ 3Δu-X3Σg-) have been studied at ambient temperature. The integrated cross section values are given for the lines of the (v′-0) bands in the A3ΣuPLU-X3Σg-, c1Σu--X3Σg-, and A′ 3Δu-X3Σg- transitions with v′ = 0-11, v′ = 2-19, and v′ = 2-12, respectively. The band oscillator strengths have been deduced and transition moments have been calculated. The total absorption values in the region of the Herzberg bands together with the photoabsorption values determined previously above the dissociation limit can be modeled by a single curve, in agreement with the continuity relationship of the cross sections through the dissociation limit.info:eu-repo/semantics/publishe

Caractérisation de la capture du VIH-1 (du récepteur DC-SIGN aux extensions trans-épithéliales des cellules dendritiques)

En tant que sentinelles du système immunitaire, les CD expriment une lectine, le DC-SIGN, présentant une forte affinité pour de nombreux pathogènes, incluant le VIH-1. L objectif premier de cette étude est d utiliser cette lectine comme outil de screening d enveloppes issues d isolats primaires de primo-infection afin d identifier une enveloppe d intérêt comme immunogène bloquant l interaction avec le DC-SIGN. Nous avons ainsi pu identifier deux mutations dans la gp41 susceptibles d amplifier l interaction DC-SIGN /gp120. Enfin, nous avons étudié la capacité de prise en charge locale et spécifique d Aspergillus fumigatus par des extensions trans-épithéliales formées par les CD au niveau des villosités de l iléon terminal murin. Notre étude souligne le rôle primordial du DC-SIGN au niveau des muqueuses monostratifiées que ce soit pour la voie de contamination homosexuelle du VIH-1 ou pour l efficacité de capture de pathogènes par les dendrites trans-épithéliales des CDAs the sentinels of the immune system, DC express a lectin DC-SIGN known to bind with high affinity a wide range of pathogens, including HIV-1. The first aim of this study is to use this lectin as a screening tool for envelopes from acute HIV-1 primary isolates in order to identify an envelope of interest that could be used as an immunogen to block the interaction with DC-SIGN. We have identified two point mutations in the gp41 susceptible to increase the DC-SIGN/gp120 interaction. At last, we have studied the local and specific uptake of Aspergillus fumigatus by trans-epithelial dendrites formed by DC in villi of the murine terminal ileum. Our study highlights the crucial role of DC-SIGN in monolayered mucosa, as suggested by the predominance of HIV-1 homosexual contamination or the efficiency of DC trans-epithelial dendrites to capture pathogensLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Abstracts of the 6th FECS Conference 1998 Lectures

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