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The expedient chemical synthesis of dual-monoubiquitinated histone through the CAET-assisted strategy is presented.

Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the central focus. Here our study on the crosstalk between H2BK34ub and Dot1L-catalyzed H3K79me suggests a novel mechanism of ubiquitination-induced nucleosome distortion to stimulate the activity of an enzyme. We determined the cryo-electron microscopy structures of Dot1L-H2BK34ub nucleosome complex and the H2BK34ub nucleosome alone. The structures reveal that H2BK34ub induces an almost identical orientation and binding pattern of Dot1L on nucleosome as H2BK120ub, which positions Dot1L for the productive conformation through direct ubiquitin-enzyme contacts. However, H2BK34-anchored ubiquitin does not directly interact with Dot1L as occurs in the case of H2BK120ub, but rather induces DNA and histone distortion around the modified site. Our findings establish the structural framework for understanding the H2BK34ub-H3K79me trans-crosstalk and highlight the diversity of mechanisms for histone ubiquitination to activate chromatin-modifying enzymes.

SummaryProteins with destabilizing N-terminal residues are degraded via K48-linked ubiquitination-dependent N-degron pathway, during which the HECT-type E3 ligase Ufd4 can further augment polyubiquitination events on these proteins to accelerate their degradation. How Ufd4 increase polyubiquitination on ubiquitinated N-degrons remains unclear. Here, we biochemically determined that Ufd4 preferentially ubiquitinates the proximal ubiquitin in K48-linked ubiquitin chain in K29-linkage specific manner and revealed high-resolution cryo-EM structures of Ufd4 accepting (E2-to-E3 state, 3.52 Å) and transferring ubiquitin-thioester (E3-to-substrate state, 3.31 Å), respectively. The N-terminal ARM region and HECT domain C-lobe of Ufd4 were identified and characterized as key structural elements that together recruit K48-linked diUb and orient Lys29 of its proximal Ub to the active cysteine of Ufd4 for K29-linked branched ubiquitination. These structures not only provide mechanistic insights into the architecture of the Ufd4 complex but also show the full picture of the Ub transferring cascades of HECT-type E3 ligase.

Mixed sedimentation is mainly a phenomenon by which siliciclastic and carbonate are mixed under a similar sedimentary environment. The study of the composition of mixed rock can reflect the sedimentary environment. The mixed sediments of the Canglangpu formation in the eastern Sichuan basin are widely developed and exhibit well exploration prospects. In this study, a classification diagram of mixed sediments suitable for the Canglangpu formation was proposed by combining lithologic characteristics with logging data. Based on the observations of typical outcrop profiles, the identification of thin sections, and drilling and geological logging data, a model was established to identify the electrical responses of the mixed sedimentary rocks in the study area. The results show that (1) the Canglangpu formation can be vertically divided into two complete transgression-regression cycles with the lower part mainly consisting of sedimentary carbonate diamictite and the upper part principally composed of clastic diamictite; (2) mixed sediments in the Canglangpu formation can be divided into six classes, namely carbonate sandstone, argillaceous sandstone, sandy carbonate rock, argillaceous carbonate rock, sandy mudstone, and Carbonate mudstone; (3) the sedimentary environment of the Canglangpu formation be divided into (a) mixed sediments in the shore, which include mixed lagoon and mixed tidal flat, (b) mixed sediments in the shallow marine shelf, which includes mixed beach bar, terrigenous detrital mixed shelf, and carbonate mixed shelf; (4) a mixed shore-mixed shelf sedimentary model has been established; it says that the mixed sediments show obvious characteristics of ring-like development around underwater paleo-heights. The formation mechanism of mixed sedimentation in the eastern Sichuan basin is mainly controlled by the change of sedimentary facies belt, and the development intensity is mainly influenced by early tectonic movement and sea-level change.

The mixed sediments of the Canglangpu Formation in the Eastern Sichuan basin are widely developed and exhibit good exploration prospects. However, relevant research and understanding in this field are still insufficient. Further research on the mixed sediments of the Canglangpu Formation is of great significance to the exploration of mixed reservoirs in this area. During the depositional period of the Canglangpu Formation, the study area experienced two complete transgression-regression cycles, with obvious stratigraphic differentiation between the upper and lower parts. The lower part consists mainly of sedimentary carbonate diamictite, while the upper part is mainly composed of sedimentary clastic diamictite, distributed in the coastal-neritic shelf sedimentary environment. A model was established to identify the electrical response of the mixed sedimentary rocks in the study area based on the observations of typical outcrop profiles, identification of thin rock sections, and drilling and geological logging data. In addition, a diagram for the classification of mixed sediments suitable for the Canglangpu Formation was proposed by combining lithofacies characteristics with logging facies data. Mixed rocks in the study area can be divided into nine classes, namely sandstone, carbonate rocks, mudstone, carbonate sandstone, argillaceous sandstone, sandy carbonate rock, argillaceous carbonate rock, sandy mudstone, and Carbonate mudstone. The study area is dominated by mixed sedimentation with a typical facies-change. In fact, the sedimentary environment of the study area is a mixed coastal-detrital and shelf-carbonate sequence. In addition, two mixed sedimentary facies, five subfacies, and 12 microfacies were identified. The mixed sediments of the Canglangpu Formation, under the special background of alternating uplifts and depressions, show obvious characteristics of ring-like development around underwater paleo-heights. The main factors controlling the formation of mixed layers are vertical tectonic movements and sea-level changes.