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What is the composition of chromatin and how is it assembled?

(Teresa Barth, Ignasi Forne, Andreas Schmidt, Moritz Völker-Albert)

The structure of chromatin is critical for many aspects of cellular physiology and is considered to be the primary medium to store epigenetic information. It is defined by the histone molecules that constitute the nucleosome, the positioning of the nucleosomes along the DNA and the non-histone proteins that associate with it. All these factors help to establish and maintain a largely DNA sequence independent but surprisingly stable structure. The conformation of chromatin is continuously challenged through processes that use DNA as a substrate such as DNA replication, repair, recombination or transcription. During all those cases chromatin is extensively disassembled and reassembled to allow the necessary factors to gain access to their substrate resulting in a very high histone turnover rates at a given genomic location. This dynamic nature of chromatin makes it even more important that the machinery mediating this continuous restructuring is well coordinated at the molecular level to maintain the epigenetic information stored in the structure.
Andreas, Ignasi, Moritz and Teresa study the proteomic composition of distinct chromatin domains, the mechanisms that operate to maintain the composition of histone modifications and the associated proteins at a given DNA locus.

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Fig. 1: STRING network of proteins assembled onto DNA in an in vitro chromatin assembly reaction.




How does the environment affect epigenetic marks?

(Esther Bux, Shiboyothi Lahiri, Jianhua Li, Shahaf Peleg)

Chromatin-modifying enzymes are though to be the authors of an epigenetic language, but the origin and meaning of the messages they write in chromatin are still mysterious. Recent studies suggesting that the effects of diet can be passed on epigenetically to offspring add weight to the idea that these enzymes act as metabolic sensors, converting changes in metabolism into stable patterns of gene expression and mediate downstream signals.
Esther, Jianhua, Shahaf and Shibo investigate how the activity of these enzymes and the modification patterns of histones are regulated by key metabolites and physiological changes such as memory formation or ageing.

fig2_ai_webFig. 2: Schematic representation of the histone H3 tail with residues that can be modified by various enzymes (E), leading to phosphorylation (P), acetylation (Ac), methylation (Me), ubiquitination (Ub), and glycosylation (Gly). Each enzyme utilizes cellular metabolites, whose availability would dictate the efficacy of the enzymatic reaction (Katada et al., Cell 2012)

How do species form and what keeps them apart?

(Thomas Gerland, Andrea Lukacz, Natalia Kochanova, Victor Solis)

Speciation involves the reproductive isolation of natural populations due to the sterility or lethality of their hybrids. The development of such an obviously maladaptive trait under the influence of natural selection is one of the main unsolved questions in evolutionary biology. In order to resolve this apparent paradox we biochemically characterized a protein complex that contains the gene products of the two speciation genes Hmr and Lhr. The two proteins are components of a larger protein complex that localizes at and close to the centromere where it represses transcription of transposable elements. In pure species this centromeric localization is important for chromosome segregation, which provides an explanation of the main driving force for the divergent evolution of their expression levels.
Andrea, Natalia, Thomas and Victor biochemically analyze the complexes and the quantitative proteomic differences and their function by combining biochemical and cell biological techniques with quantitative proteomics and large-scale sequencing.

fig3_ai_webFig. 3: Two stylized fly species are arranged in front of a spindle to resemble a mitotic figure. This picture illustrates the major role of a novel centromeric protein complex in species separation and mitotic division. The dark color of one fly also depicts the role of this complex in forming transcriptionally repressive “dark” heterochromatin (Cover picture from Thomae et al., 2013, Dev Cell)