SummaryTET enzymes including TET1, 2 and 3 convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC)1 and regulate gene transcription2-5. However, this molecular mechanism by which TET family enzymes regulate gene transcription remains elusive5-6. Here, using protein affinity purification, we searched for functional partners of TET proteins, and found that TET2 and TET3 associate with OGT, an enzyme that by itself catalyzes O-GlcNAcylation in vivo7-8. TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription starting sites (TSS). Down-regulation of TET2 reduces the amount of H2B S112 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the gene transcription regulation.

Summary Ubiquitin-like proteins have been shown to be covalently conjugated to targets. However, the functions of these ubiquitin-like proteins are largely unknown. Here, we have screened most known ubiquitin-like proteins after DNA damage and found that NEDD8 is involved in the DNA damage response. Following various DNA damage stimuli, NEDD8 accumulated at DNA damage sites, and this accumulation was dependent on an E2 enzyme UBE2M and an E3 ubiquitin ligase RNF111. We further found that histone H4 was polyneddylated in response to DNA damage, and NEDD8 was conjugated to the N-terminal lysine residues of H4. Interestingly, the DNA damage-induced polyneddylation chain could be recognized by the MIU (Motif Interacting with Ubiquitin) domain of RNF168. Loss of DNA damage-induced neddylation negatively regulated DNA damage-induced foci formation of RNF168 and its downstream functional partners, such as 53BP1 and BRCA1, thus affecting the normal DNA damage repair process.

A nanocrystal heterojunction LaVO4TiO2 visible light photocatalyst has been successfully prepared by a simple coupled method. The catalyst was characterized by powder X-ray diffraction, nitrogen adsorption-desorption, transmission electron microscopy, UV-vis diffuse reflectance spectroscopy, X-ray photoelectron spectra, photoluminescence, and electrochemistry technology.The results showed that the prepared nanocomposite catalysts exhibited strong photocatalytic activity for decomposition of benzene under visible light irradiation with high photochemical stability. The enhanced photocatalytic performance of LaVO4/TiO2 may be attributed to not only the matched band potentials but also interconnected heterojunction of LaVO4 and TiO2 nanoparticles.

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Protein ubiquitination is a critical component of the DNA damage response. To study the mechanism of the DNA damage-induced ubiquitination pathway, we analyzed the impact of the loss of two E3 ubiquitin ligases, RNF8 and Chfr. Interestingly, DNA damage-induced ATM activation is suppressed in RNF8 and Chfr double-deficient (DKO) cells, and DKO mice develop thymic lymphomas that are nearly diploid but harbor clonal chromosome translocations. Moreover, DKO mice and cells are hypersensitive to ionizing radiation. We show evidence that RNF8 and Chfr synergistically regulate histone ubiquitination to control histone H4K16 acetylation through MRG15-dependent acetyltransferase complexes. Through these complexes, RNF8 and CHFR affect chromatin relaxation and modulate ATM activation and DNA damage response pathways. Collectively, our findings demonstrate that two chromatin remodeling factors, RNF8 and Chfr, function together to activate ATM and maintain genomic stability in vivo.