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Characterization of the role of histone H1 and its post-translational modifications in the functional regulation of chromatin


Histone H1 participates in both the establishment and stabilization of high-order of chromatin organization through its binding to the internucleosomal DNA. H1 seems to play an important role in regulation of chromatin functions, and particularly in the regulation of gene expression and chromosome condensation.

However, our understanding of H1 function is based mainly on in vitro studies and we do not understand completely how H1 exerts it function in vivo or how it coordinates with the rest of the chromatin machinery. This is in part a consequence of the high complexity of H1 present in the majority of eukaryotes analyzed so far.

The existence of multiple isoforms together with intrinsic difficulties to develop specific antibodies against each one of them, hinders enormously the study of H1 contribution to chromatin regulation in vivo. Histone H1, like the rest of histones, is regulated by certain post-translational modifications. However, we still do not know the whole set of modifications of H1 and their functional relevance in control of epigenetic phenomena of transcriptional regulation, chromatin structure, cell cycle control and differentiation.

This project aims to elucidate the in vivo role of histone H1 and its post-translational modifications in the regulation of chromatin functions. We intend to use Drosophila melanogaster as experimental model for our studies, since in contrast to vertebrates and some other Drosophila species, the D. melanogaster multi-copy gene His1 codifies for a single isoform. Additionally, Drosophila offers obvious technical advantages from a biochemical and genetic point of view.

The aim of the project will be achieved by different approaches like the identification and in vivo and in vitro characterization of post-translational modifications in H1, the analysis of the effects of the loss of H1, and the study of the functional relationship between H1 and the rest of the chromatin machinery.

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