Regulating specificity in enhancer-promoter communication.

Enhancers are cis-regulatory elements that can activate transcription remotely to regulate a specific pattern of a gene's expression. Genes typically have many enhancers that are often intermingled in the loci of other genes. To regulate expression, enhancers must therefore activate their correct promoter while ignoring others that may be in closer linear proximity. In this review, we discuss mechanisms by which enhancers engage with promoters, including recent findings on the role of cohesin and the Mediator complex, and how this specificity in enhancer-promoter communication is encoded. Genetic dissection of model loci, in addition to more recent findings using genome-wide approaches, highlight the core promoter sequence, its accessibility, cofactor-promoter preference, in addition to the surrounding genomic context, as key components.

Transvection regulates the sex-biased expression of a fly X-linked gene.

Sexual dimorphism in animals results from sex-biased gene expression patterns. These patterns are controlled by genetic sex determination hierarchies that establish the sex of an individual. Here we show that the male-biased wing expression pattern of the Drosophila biarmipes gene yellow, located on the X chromosome, is independent of the fly sex determination hierarchy. Instead, we find that a regulatory interaction between yellow alleles on homologous chromosomes (a process known as transvection) silences the activity of a yellow enhancer functioning in the wing. Therefore, this enhancer can be active in males (XY) but not in females (XX). This transvection-dependent enhancer silencing requires the yellow intron and the chromatin architecture protein Mod(mdg4). Our results suggest that transvection can contribute more generally to the sex-biased expression of X-linked genes.

Relevance and mechanisms of transvection.

Transvection, the functional interaction between homologous alleles, was first described in Drosophila in the 1950's. While transvection has been documented in a growing list of genes, using mutant alleles or synthetic constructs, in Drosophila and other organisms, the extent of its relevance to gene expression in physiological conditions has remained questionable. The molecular mechanisms underlying transvection are still largely unexplored, although hints suggest a link with the general machinery that controls the genome organization in the nucleus. In this review, we discuss recent results establishing the relevance of transvection for proper gene regulation, and in particular for the sexually dimorphic regulation of the Drosophila X-linked gene yellow. We also discuss the role that DNA insulator sequences and chromatin architectural proteins play in bringing in proximity homologous alleles, and how they may contribute to interallelic gene regulation.

La transvection, l'interaction fonctionnelle entre des allèles homologues, a été décrite pour la première fois chez la drosophile dans les années 1950. Bien que la transvection ait été documentée pour une liste croissante de gènes, en utilisant des allèles mutants ou des constructions synthétiques, chez la drosophile et d'autres organismes, l'étendue de sa pertinence pour la régulation de l'expression des gènes dans des conditions physiologiques reste une question ouverte. Les mécanismes moléculaires qui sous-tendent la transvection sont encore largement inexplorés, bien que des indices suggèrent un lien avec la machinerie générale qui contrôle l'organisation du génome dans le noyau. Dans cette revue, nous discutons des résultats récents établissant la pertinence de la transvection pour la régulation correcte des gènes, et en particulier pour la régulation sexuellement dimorphique du gène yellow qui est porté par le chromosome X de la drosophile. Nous discutons également du rôle que jouent les séquences d'ADN isolatrices et les protéines architecturales de la chromatine dans le rapprochement des allèles homologues, et comment elles peuvent contribuer à la régulation interallélique des gènes.