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Histone modifications are involved in the regulation of chromatin-based processes, including transcription, DNA replication and repair1–5. Among them, histone acetylation and deacetylation are usually correlated with transcription activation and repression, respectively6. The Set2-Rpd3S pathway maintains hypoacetylation states of actively transcribed chromatin regions to suppress cryptic transcription initiation7–9. During this process, the histone deacetylase (HDAC) complex Rpd3S is recruited to nucleosomes which are methylated at lysine 36 residue of histone H3 (H3K36me) by histone methyltransferase Set27,9. However, how the five unique subunits of Rpd3S are assembled and coordinated to recognize nucleosomal substrates and exert its deacetylation function remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structure of Saccharomyces cerevisiae Rpd3S deacetylase bound to H3K36me3-modified nucleosome at 3.1 Å resolution. It reveals that Sin3 and Rco1 subunits orchestrate the assembly of the complex and mediate its contact with nucleosome at multiple sites. In addition, the chromodomain (CHD) of Eaf3 subunit recognizes the H3K36me3 marker and contacts both nucleosomal and linker DNA. The structure not only unravels the architecture of the Rpd3S complex, but also sheds light on the structural basis of its nucleosome targeting and function.

In actinobacteria, post-translational modification of proteins with prokaryotic ubiquitin-like protein Pup targets them for degradation by a bacterial proteasome assembly consisting of the 20S core particle (CP) and the mycobacterial proteasomal ATPase (Mpa). Modification of hundreds of cellular proteins with Pup at specific surface lysines is carried out by a single Pup-ligase (PafA, proteasome accessory factor A). Pupylated substrates are recruited to the degradative pathway by binding of Pup to the N-terminal coiled-coil domains of Mpa. Alternatively, pupylation can be reversed by the enzyme Dop (deamidase of Pup). Although pupylated substrates outcompete free Pup in proteasomal degradation, potential discrimination of the degradation complex between the various pupylated substrates has not been investigated. Here we show that Mpa binds stably to an open-gate variant of the proteasome (oCP) and associates with bona fide substrates with highly similar affinities. The proteasomal degradation of substrates differing in size, structure and assembly state was recorded in real-time, showing that the pupylated substrates are processed by the Mpa-oCP complex with comparable kinetic parameters. Furthermore, the members of a complex, pupylated proteome (pupylome) purified from Mycobacterium smegmatis are degraded evenly as followed by western blotting. In contrast, analysis of the depupylation behavior of several pupylome members suggests substrate-specific differences in enzymatic turnover, leading to the conclusion that largely indiscriminate degradation competes with differentiated depupylation to control the ultimate fate of pupylated substrates., PLoS ONE, 14 (4), ISSN:1932-6203

This paper focuses on a particularly crucial aspect of haptic perception: the ability to temporarily store and manipulate haptic sensory information-a capacity termed haptic working memory (HWM). Despite the importance of HWM, the extent and nature of its limitations are largely unknown. Recent research however, has demonstrated that an information-theoretic analysis is able to provide a quantitative definition of working memory capacity for other sensory modalities (visual), and is able to yield novel predictions for human performance. Here we apply this framework to the results of a psychophysical experiment on HWM for object width. This analysis is framed around rate-distortion theory, a branch of information theory that provides optimal bounds on the accuracy of information transmission subject to a fixed information capacity. We demonstrate that a simple model developed from this framework provides an excellent account of the empirical data.