TAXi-ch · Determination of transcription factor cooperativity driving expression from the inactive X chromosome

Determination of transcription factor cooperativity driving expression from the inactive X chromosome

In mammals, in order to compensate for the double dose of X-linked genes between XX females and XY males, female cells inactivate one of the X chromosomes during embryonic development. This process triggers chromosome-wide silencing of most genes on one X chromosome. Once the inactive X (Xi) chromosome has been established, its silent state is preserved during subsequent cell divisions. However, there is a small percentage of genes for which expression is detectable from the Xi chromosome (so-called escapees), albeit usually at lower levels than from the active X (Xa) chromosome in general. Among these genes, several have been associated with neurological, metabolic and autoimmune disorders, and considering the increased incidence of some of these pathologies in females, their proper regulation is likely to be important for female physiology. Indeed, for some escapee genes this has been directly shown (e.g. the implication of TLR7 escape from XCI in systemic lupus erythematosus). Escapees have been identified in several species and tissues, yet, there is a lack of knowledge about their regulation and their expression dynamics during the silencing process. For instance, it is not known if genes expressed from the Xi chromosome are regulated by shared regulatory networks than their counterparts in the Xa chromosome or if the transcription factors (TFs) involved in these networks play the exact same roles. This is important in order to understand how escapee genes are expressed from the Xi, and whether this can ultimately help in detecting or treating associated disorders. In consequence, the TAXi-ch project was designed to shed light into the regulators of escapees and their interplay by: 1. Identifying TFs involved in the regulation of expression from the Xi chromosome and assessing their contribution. 2. Generating gene regulatory networks of X-linked genes. TAXi-ch advances the current knowledge of gene regulation in the Xi chromosome by identifying candidate regulators that can be explored in the future, and by investigating the role and mechanism of action of one of them. Moreover, the fellow (Yuvia A. Pérez-Rico) improved professional skills that are relevant to become a competitive candidate for leadership positions in Europe.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз