Le site aurignacien de plein-air de Combemenue à Brignac-la-Plaine (Corrèze) : apport de la géochéologie et de l’étude de l’industrie lithique à la compréhension des processus taphonomiques

Le site paléolithique de Combemenue en Corrèze a livré un niveau d’occupation d’Aurignacien récent enfoui à faible profondeur, sur un replat près du sommet d’un versant. Le contexte de faible enfouissement laissant suspecter des perturbations significatives du niveau archéologique dues à une longue exposition aux agents naturels en surface ou en subsurface du sol, une étude taphonomique détaillée a été entreprise. Différents points ont été examinés : la distribution spatiale du matériel, la disposition des objets (fabrique), leur granulométrie, leur état de surface ainsi que les remontages. Les résultats obtenus ont été confrontés de manière à proposer un scénario qui rende compte au mieux de l’ensemble des observations faites sur le site. Cette étude indique que l’assemblage lithique originel a subi un appauvrissement sélectif en petits éléments sous l’action du ruissellement. Simultanément, il est possible qu’une partie du matériel de plus grande taille initialement présent ait été soustrait du site par les mécanismes sédimentaires. Ces modifications ont eu des répercussions sur la distribution spatiale des vestiges. Celle-ci se caractérise par une absence de concentration claire, tant lorsqu’on considère la répartition de l’ensemble du matériel que celle de catégories particulières d’objets. Une diffusion progressive des vestiges par le ruissellement ou les phénomènes périglaciaires rend bien compte des transformations observées. En revanche, les déplacements n’ont pas entraîné d’altération physique importante des pièces, dont la majorité ne porte pas de stigmate postérieur à sa production ou son utilisation par les Aurignaciens. Les transformations décrites ici pour le site de Combemenue sont probablement représentatives de celles subies par un grand nombre de sites paléolithiques localisés sur une pente négligeable dans un contexte géomorphologique peu favorable à un enfouissement rapide.An Upper Aurignacian level located on a hilltop flat surface has been found at Combemenue (Brignac-la-Plaine, Corrèze, France) during field surveys along the A89 highway. Geomorphological evidence, and particularly the shallow depth of the level, strongly suggests that it has undergone significant perturbation due to a long-lasting exposure to sedimentary and pedological processes at the soil surface or subsurface. Therefore, a detailed taphonomic study has been made to evaluate the impact of natural processes in site patterning. It involves examination of the spatial distribution of the artefacts, their orientation and dip (fabric), their size distribution, their alteration and refits. The results have been compared to the data derived from the techno-economical analysis. This study indicates that the lithic assemblage has undergone a selective impoverishment in small-sized artefacts as the result of surface wash. A part of the coarser artefacts may have been also removed from the site by the same processes. The lack of any clear artefact concentration indicates that the spatial distribution has been modified significantly. This can be adequately described by a model of progressive diffusion of the artefacts by surface wash or periglacial processes. By contrast, the movements did not provoke strong physical alteration of the pieces. The Combemenue site is thought to be representative of a number of palaeolithic sites located in similar geomorphological contexts, which are characterized by low sedimentation rates

Identification, replication and characterization of epigenetic remodelling in the aging genome:A cross population analysis

Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWE

Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer.

Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway

Epigenetic Regulation of Fatty Acid Amide Hydrolase in Alzheimer Disease

OBJECTIVE: Alzheimer disease (AD) is a progressive, degenerative and irreversible neurological disorder with few therapies available. In search for new potential targets, increasing evidence suggests a role for the endocannabinoid system (ECS) in the regulation of neurodegenerative processes. METHODS: We have studied the gene expression status and the epigenetic regulation of ECS components in peripheral blood mononuclear cells (PBMCs) of subjects with late-onset AD (LOAD) and age-matched controls (CT). RESULTS: We found an increase in fatty acid amide hydrolase (faah) gene expression in LOAD subjects (2.30 ± 0.48) when compared to CT (1.00 ± 0.14; *p<0.05) and no changes in the mRNA levels of any other gene of ECS elements. Consistently, we also observed in LOAD subjects an increase in FAAH protein levels (CT: 0.75 ± 0.04; LOAD: 1.11 ± 0.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.80 ± 8.73; LOAD: 125.10 ± 4.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.90 ± 4.60%; LOAD: 41.20 ± 4.90%; *p<0.05). CONCLUSIONS: Present findings suggest the involvement of FAAH in the pathogenesis of AD, highlighting the importance of epigenetic mechanisms in enzyme regulation; they also point to FAAH as a new potential biomarker for AD in easily accessible peripheral cells

DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing

Tissue specific patterns of methylated cytosine residues vary with age, can be altered by environmental factors, and are often abnormal in human disease yet the cellular consequences of DNA methylation are incompletely understood. Although the bodies of highly expressed genes are often extensively methylated in plants, the relationship between intragenic methylation and expression is less clear in mammalian cells. We performed genome-wide analyses of DNA methylation and gene expression to determine how the pattern of intragenic methylation correlates with transcription and to assess the relationship between methylation of exonic and intronic portions of the gene body. We found that dense exonic methylation is far more common than previously recognized or expected statistically, yet first exons are relatively spared compared to more downstream exons and introns. Dense methylation surrounding the transcription start site (TSS) is uncoupled from methylation within more downstream regions suggesting that there are at least two classes of intragenic methylation. Whereas methylation surrounding the TSS is tightly linked to transcriptional silencing, methylation of more downstream regions is unassociated with the magnitude of gene expression. Notably, we found that DNA methylation downstream of the TSS, in the region of the first exon, is much more tightly linked to transcriptional silencing than is methylation in the upstream promoter region. These data provide direct evidence that DNA methylation is interpreted dissimilarly in different regions of the gene body and suggest that first exon methylation blocks transcript initiation, or vice versa. Our data also show that once initiated, downstream methylation is not a significant impediment to polymerase extension. Thus, the consequences of most intragenic DNA methylation must extend beyond the modulation of transcription magnitude