Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark

Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements

The Diversity of Trajectories of Large Housing Estates in Madrid, Spain

Public and private housing developments between 1940 and 1990 shaped the City of Madrid by differentiating urban area types according to social composition, location and development type. Spanish housing policies over these decades fostered public housing stock that, unlike in European cities, ended up being transformed into owned rather than rented homes; closely linking certain disadvantaged groups to the most vulnerable areas of the city. In this chapter, current processes of physical and social vulnerability are analysed using data from the 2001 and 2011 Population and Housing Censuses using a multivariate analysis. Our analysis differentiates between two stages of social housing estates in Madrid (under Francoism and in the democratic period) and private housing developments. These analyses show significant differences both in the trajectories of each of the types analysed in relation to contemporary vulnerability processes, as well as in the composition of the population that resides in them. Lastly, we examine challenges and proposals for the future of these urban areas, considering their social composition and the urban policies that seek to rebalance Madrid’s neighbourhoods and paying attention to the insertion of the immigrant population into the most vulnerable neighbourhoods of the city.Depto. de Sociología AplicadaFac. de Estudios EstadísticosFac. de Ciencias Políticas y SociologíaTRUEpu