RESUMO
DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1-a component of the E3 ligase complex involved in HIV regulation-is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.
Assuntos
HIV-1 , Histona-Lisina N-Metiltransferase , Histonas , NF-kappa B , Ubiquitina-Proteína Ligases , Humanos , HIV-1/fisiologia , HIV-1/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , NF-kappa B/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Repetição Terminal Longa de HIV/genética , Células HEK293 , Ativação Viral , Metilação , Fator de Necrose Tumoral alfa/metabolismo , Infecções por HIV/virologia , Infecções por HIV/metabolismo , Lisina/metabolismo , Proteínas Serina-Treonina QuinasesRESUMO
Plant protein films are a research hotpot in the current food packaging field for their renewable and bio-compatibility, and further improving the physicochemical properties of plant protein films in combination with biodegradable materials is of great significance. In this study, we selected cellulose nanocrystals (CNC) to modify the protein films with soybean protein isolate (SPI), wheat gluten protein (WGP), and Zein, and the physicochemical properties were studied. The results showed that the hardness and opacity of Zein-based films decreased by 16.61% and 54.12% with the incorporation of CNC, respectively. The SPI-based films performed with lower hardness and higher tensile strength. The thickness and opacity of WGP-based films increased by 39.76% and 214.38% after combination with CNC, respectively. Accordingly, this study showed that CNC could largely modify the physicochemical properties of the plant protein films, which provided a reference for the preparation of modified plant protein films using biodegradable materials.