Herein, we present a new strategy for the synthesis of 2D porous MoP/Mo2N heterojunction nanosheets based on the pyrolysis of 2D [PMo12O40]3−‐melamine (PMo12‐MA) nanosheet precursor from a polyethylene glycol (PEG)‐mediated assembly route. The heterostructure nanosheets are ca. 20 nm thick and have plentiful pores (<5 nm). These structure features offer advantages to promote the HER activity, including the favorable water dissociation kinetics around heterojunction as confirmed by theoretical calculations, large accessible surface of 2D nanosheets, and enhanced mass‐transport ability by pores. Consequently, the 2D porous MoP/Mo2N heterojunction nanosheets exhibit excellent HER activity with low overpotentials of 89, 91 and 89 mV to achieve a current density of 10 mA cm−2 in alkaline, neutral and acidic electrolytes, respectively. The HER performance is superior to the commercial Pt/C at a current density >55 mA cm−2 in neutral medium and >190 mA cm−2 in alkaline medium.

The tandem PHD finger-bromodomain, found in many chromatin-associated proteins, has an important role in gene silencing by the human co-repressor KRAB-associated protein 1 (KAP1). Here we report the three-dimensional solution structure of the tandem PHD finger-bromodomain of KAP1. The structure reveals a distinct scaffold unifying the two protein modules, in which the first helix, α Z , of an atypical bromodomain forms the central hydrophobic core that anchors the other three helices of the bromodomain on one side and the zinc binding PHD finger on the other. A comprehensive mutation-based structure-function analysis correlating transcriptional repression, ubiquitin-conjugating enzyme 9 (UBC9) binding and SUMOylation shows that the PHD finger and the bromodomain of KAP1 cooperate as one functional unit to facilitate lysine SUMOylation, which is required for KAP1 co-repressor activity in gene silencing. These results demonstrate a previously unknown unified function for the tandem PHD finger-bromodomain as an intramolecular small ubiquitin-like modifier (SUMO) E3 ligase for transcriptional silencing.Chemical modifications of chromatin on the DNA (for example, methylation of cytosine) and DNA-packing histones (for example, acetylation, methylation, phosphorylation, ubiquitination and SUMOylation) are important in the epigenetic control of gene transcription in response to physiological and environmental stimuli [1][2][3] . An emerging model suggests that there is an 'epigenetic code' embedded within chromatin to signify regions of distinct nuclear activities, such as heterochromatin formation or transcriptional activation [4][5][6] . It is thought that the epigenetic code is established by chromatin-modifying enzymes and interpreted by proteins that bind the chromatin in a modification-sensitive manner. The discovery of methyl-CpG binding domains 7 , bromodomains as acetyllysine binding The tandem bromodomain-PHD finger of the human transcriptional coactivator p300/CBP has been shown to be interdependent in interactions with nucleosomes 27 . A more common, reversely connected motif, the PHD finger-bromodomain, is found in many chromatinassociated proteins including histone lysine methyl-transferase MLL1 (ref. 28), Williams syndrome transcription factor (WSTF) in the chromatin-remodeling complex WINAC 29 , and the TIF1 family proteins (α, β, γ and δ; note that TIF1β is also known as KAP1 or TRIM28) 30 . This tandem PHD finger-bromodomain is also found in Sp140, a leukocytespecific protein in the nuclear body that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection 31 . Mutations of PHD fingers, particularly those that disrupt zinc coordination, have been linked to tumor formation and genetic disorders 32 .More recently, it has been reported that the PHD finger of the human co-repressor KAP1 functions as a unique SUMO E3 ligase that is required for KAP1's gene transcription repression activity 33 .To understand its molecular function in gene silencing, we solved the three-dim...

EBNA1 is the only nuclear Epstein-Barr virus (EBV) protein expressed in both latent and lytic modes of infection. While EBNA1 is known to play several important roles in latent infection, the reason for its continued expression in lytic infection is unknown. Here we identified two roles for EBNA1 in the reactivation of latent EBV to the lytic cycle in epithelial cells. First, EBNA1 depletion in latently infected cells was shown to positively contribute to spontaneous EBV reactivation, showing that EBNA1 has a role in suppressing reactivation. Second, when the lytic cycle was induced, EBNA1 depletion decreased lytic gene expression and DNA amplification, showing that it positively contributed to lytic infection. Since we have previously shown that EBNA1 disrupts promyelocytic leukemia (PML) nuclear bodies, we investigated whether this function could account for the effects of EBNA1 on lytic infection by repeating the experiments with cells lacking PML proteins. In the absence of PML, EBNA1 did not promote lytic infection, indicating that the EBNA1-mediated PML disruption is responsible for promoting lytic infection. In keeping with this conclusion, PML silencing was found to be sufficient to induce the EBV lytic cycle. Finally, by generating cells with single PML isoforms, we showed that individual PML isoforms were sufficient to suppress EBV lytic reactivation, although PML isoform IV (PML IV) was ineffective because it was most efficiently degraded by EBNA1. Our results provide the first function for EBNA1 in lytic infection and show that EBNA1 interactions with PML IV lead to a loss of PML nuclear bodies (NBs) that promotes lytic infection.