Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences

Analysis of the evolutionary dynamics of target gene batteries controlled by 16 different transcription factors reveals stable ancestral cores and highly dynamic regulatory sequence

Uncoupling Time and Space in the Collinear Regulation of Hox Genes

During development of the vertebrate body axis, Hox genes are transcribed sequentially, in both time and space, following their relative positions within their genomic clusters. Analyses of animal genomes support the idea that Hox gene clustering is essential for coordinating the various times of gene activations. However, the eventual collinear ordering of the gene specific transcript domains in space does not always require genomic clustering. We analyzed these complex regulatory relationships by using mutant alleles at the mouse HoxD locus, including one that splits the cluster into two pieces. We show that both positive and negative regulatory influences, located on either side of the cluster, control an early phase of collinear expression in the trunk. Interestingly, this early phase does not systematically impact upon the subsequent expression patterns along the main body axis, indicating that the mechanism underlying temporal collinearity is distinct from those acting during the second phase. We discuss the potential functions and evolutionary origins of these mechanisms, as well as their relationship with similar processes at work during limb development

Etats généraux de la presse écrite - Livre vert

Les Etats généraux de la presse écrite, lancés par le président de la République le 2 octobre 2008, ont eu pour mission d\u27apporter des réponses aux difficultés économiques que rencontre la presse écrite, notamment face au développement de l\u27internet et des journaux gratuits. Coordonnées par le ministère de la culture et de la communication, les réunions thématiques des quatre pôles de réflexions, respectivement consacrés aux métiers du journalisme, au processus industriel de la presse, à l\u27impact d\u27internet et aux questions de société ont eu pour objectif d\u27établir un diagnostic complet. Plus de 150 professionnels y ont participé durant trois mois. A l\u27issue de 70 heures d\u27auditions et de débats, les chefs de pôles ont émis des propositions qui ont permis d\u27élaborer ce Livre vert présentant plus de 90 recommandations

Characterization of mouse Dactylaplasia mutations: a model for human ectrodactyly SHFM3

SHFM3 is a limb malformation characterized by the absence of central digits. It has been shown that this condition is associated with tandem duplications of about 500 kb at 10q24. The Dactylaplasia mice display equivalent limb defects and the two corresponding alleles (Dac 1j and Dac 2j ) map in the region syntenic with the duplications in SHFM3. Dac 1j was shown to be associated with an insertion of an unspecified ETn-like mouse endogenous transposon upstream of the Fbxw4 gene. Dac 2j was also thought to be an insertion or a small inversion in intron 5 of Fbxw4, but the breakpoints and the exact molecular lesion have not yet been characterized. Here we report precise mapping and characterization of these alleles. We failed to identify any copy number differences within the SHFM3 orthologous genomic locus between Dac mutant and wild-type littermates, showing that the Dactylaplasia alleles are not associated with duplications of the region, in contrast with the described human SHFM3 cases. We further show that both Dac 1j and Dac 2j are caused by insertions of MusD retroelements that share 98% sequence identity. The differences between the nature of the human and mouse genomic abnormalities argue against models proposed so far that either envisioned SHFM3 as a local trisomy or Dac as a mutant allele of Fbxw4. Instead, both genetic conditions might lead to complex alterations of gene regulation mechanisms that would impair limb morphogenesis. Interestingly, the Dac 2j mutation occurs within a highly conserved element that may represent a regulatory sequence for a neighboring gen

Associations of social and material deprivation with tobacco, alcohol, and psychotropic drug use, and gender: a population-based study

International audienceBACKGROUND: The aim was to assess the relationships between social and material deprivation and the use of tobacco, excessive alcohol and psychotropic drugs by both sexes and in various age groups. Greater knowledge concerning these issues may help public health policy-makers design more effective means of preventing substance abuse. METHODS: The sample comprised 6,216 people aged > or 15 years randomly selected from the population in north-eastern France. Subjects completed a post-mailed questionnaire covering socio-demographic characteristics, occupation, employment, income, smoking habit, alcohol abuse and "psychotropic" drug intake (for headache, tiredness, nervousness, anxiety, insomnia). A deprivation score (D) was defined by the cumulative number of: low educational level, manual worker, unemployed, living alone, nationality other than western European, low income, and non-home-ownership. Data were analysed using adjusted odds ratios (ORa) computed with logistic models. RESULTS: Deprivation was common: 37.4% of respondents fell into category D = 1, 21.2% into D = 2, and 10.0% into D > or 3a re men than women reported tobacco use (30.2% vs. 21.9%) and alcohol abuse (12.5% vs. 3.3%), whereas psychotropic drug use was more common among women (23.8% vs. 41.0%). Increasing levels of deprivation were associated with a greater likelihood of tobacco use (ORa vs. D = 0: 1.16 in D = 1, 1.49 in D = 2, and 1.93 in D > or = 3), alcohol abuse (1.19 in D = 1, 1.32 in D = 2, and 1.80 in D > or = 3) and frequent psychotropic drug intake (1.26 in D = 1, 1.51 in D = 2, and 1.91 in D > or = 3). These patterns were observed in working/other non-retired men and women (except for alcohol abuse in women). Among retired people, deprivation was associated with tobacco and psychotropic drug use only in men. CONCLUSION: Preventive measures should be designed to improve work conditions, reduce deprivation, and help deprived populations to be more aware of risk and to find remedial measures

TATTOO-seq delineates spatial and cell type-specific regulatory programs in the developing limb

The coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we developed and applied an unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs underlying the emergence of specialized cell types during mouse limb development and their spatial integration. We identify multiple transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, suggesting two parallel yet highly interconnected regulatory systems.We demonstrate that the embryonic limb undergoes a complex multiscale reorganization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, alterations of preexisting cell states' molecular identities, and changes in their relative spatial distribution. Our study shows how multidimensional single-cell, spatially resolved molecular atlases can allow the deconvolution of spatial identity and cell fate and reveal the interconnected genetic networks that regulate organogenesis and its reorganization upon genetic alterations

A systematic enhancer screen using lentivector transgenesis identifies conserved and non-conserved functional elements at the olig1 and olig2 locus

Finding sequences that control expression of genes is central to understanding genome function. Previous studies have used evolutionary conservation as an indicator of regulatory potential. Here, we present a method for the unbiased in vivo screen of putative enhancers in large DNA regions, using the mouse as a model. We cloned a library of 142 overlapping fragments from a 200 kb-long murine BAC in a lentiviral vector expressing LacZ from a minimal promoter, and used the resulting vectors to infect fertilized murine oocytes. LacZ staining of E11 embryos obtained by first using the vectors in pools and then testing individual candidates led to the identification of 3 enhancers, only one of which shows significant evolutionary conservation. In situ hybridization and 3C/4C experiments suggest that this enhancer, which is active in the neural tube and posterior diencephalon, influences the expression of the Olig1 and/or Olig2 genes. This work provides a new approach for the large-scale in vivo screening of transcriptional regulatory sequences, and further demonstrates that evolutionary conservation alone seems too limiting a criterion for the identification of enhancers