A new route for histone deposition into chromatin
Thomas Küntziger has published the article "PML protein organizes heterochromatin domains where it regulates histone H3.3 deposition by ATRX/DAXX" in Genome Research.
Organization of the genetic material in eukaryotic cells results from the close association of a variety of proteins including histones with DNA, thus forming chromatin. During the last decades, a fundamental concept has emerged whereby local variations in the post-translational modification pattern of histone proteins determine to a large extent the structural and functional properties of the corresponding chromatin regions. In addition to histone post-translational modifications, another major contributor to this compartmentalization of chromatin is the nature of the histone proteins themselves. Most histone proteins in higher eukaryotes are coded by more than one gene as is the case for example with histone H3.3, a variant form of the classical histone H3. Many research efforts are now directed towards understanding the contribution of various histone variants in determining the properties of the chromatin segments in which they are incorporated, as well as identifying the mechanisms responsible for targeted histone variant delivery at specific chromatin sites.
In a recent paper (Delbarre et al., 2017, Genome Research), Associate Professor Thomas Küntziger at the Department of Oral Biology, Faculty of Dentistry in collaboration with the group of Professor Philippe Collas (Department of Molecular Medicine, Faculty of Medicine) has studied the contribution of Promyelocytic Leukemia (PML) protein in routing H3.3 to chromatin. The authors show megabase-sized chromatin domains associated with PML protein, which harbor markers typical of chromatin with low transcriptional activity (heterochromatin). Presence of PML at these PML-associated domains (PADs) is required for maintenance of a heterochromatin state. PML also affects the delivery of new H3.3 molecules at these domains, by targeting the histone chaperone machinery responsible for site-specific loading on chromatin. In addition to the organization of chromosome domains, these results also suggest that PML may be involved in the clustering of functionally related genes, possibly as a mechanism to coregulate expression and/or repression.
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