Biology subjects

Sung, S.

Publications and source records attributed to Sung, S..

3 recordsLinked to original sources

bioRxiv2020

Direct phosphorylation of HY5 by SPA1 kinase to regulate photomorphogenesis in Arabidopsis

ELONGATED HYPOCOTYL5 (HY5) is a key transcription factor which promotes photomorphogenesis by regulating complex downstream growth programs. Previous studies suggest that the regulation of HY5 mainly depends on the CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) - SUPPRESSOR OF PHYTOCHROME A-105 (SPA) E3 ubiquitin ligase complex, which degrades positively acting transcription factors of light signaling to repress photomorphogenesis in the dark. SPA proteins function not only as a component of the E3 ubiquitin ligase complex but also as a kinase of PHYTOCHROME INTERACTING FACTOR1 (PIF1) through its N-terminal kinase domain. Here, we show that HY5 is a new substrate of SPA1 kinase. SPA1 can directly phosphorylate HY5 in vitro and in vivo. We also demonstrate that unphosphorylated HY5 strongly interacts with both COP1 and SPA1 than phosphorylated HY5, is the preferred substrate for degradation, whereas phosphorylated HY5 is more stable in the dark. In addition, unphosphorylated HY5 actively binds to the target promoters, and is physiologically more active form. Consistently, the transgenic plants expressing unphosphorylated mutant of HY5 displays enhanced photomorphogenesis. Collectively, our study revealed that SPA1 fine-tunes the stability and the activity of HY5 to regulate photomorphogenesis.

plant biology↗

bioRxiv2020

VIL1, a Polycomb-associated protein, modulates high ambient temperature response via H3K27me3 and H2A.Z in Arabidopsis thaliana

Adapting to the everchanging environment is key to a successful life for an organism. Eukaryotes reprogram their transcriptome in order to adapt to an unfavorable environment. To achieve this reprogramming, plants and animals employ multiple responses including epigenetic regulation. In the search for mutations compromised in high ambient temperature response, we found that VIL1, a PHD finger protein displays aberrant development at high temperature. RNA-seq analysis shows that vil1 fails to downregulate heat suppressed genes. H2A.Z ChIP-seq showed that unlike wild type, vil1 fails to evict H2A.Z from heat responsive genes. We also found that vil1 suppresses constitutive thermo-morphogenic phenotype of arp6. Supporting this phenotype, RNA-seq analysis revealed that constitutive heat responsive transcriptome of arp6 reverted back to the wild-type levels in arp6vil1. This observation suggests an antagonistic relationship between VIL1 and ARP6. We found that this antagonism can be explained in part by interaction between H3K27me3 and H2A.Z.

plant biology↗

bioRxiv2019

A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques

We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbits and rhesus macaque models. A dose-ranging study in rabbits demonstrated dose-dependent pharmacokinetics and local inflammation up to severe necrosis around the active implants. The matched placebos showed normal wound healing and fibrous tissue encapsulation of the implant. We designed a second implant with a lower release rate and flux of TAF and achieved a median cellular level of tenofovir diphosphate of 42 fmol per 106 rhesus macaque peripheral blood mononuclear cells at a dose of 10 {micro}g/kg/day. This dose and flux of TAF also resulted in adverse local inflammation and necrosis near the implant in rhesus macaques. Inflammation in the primates was markedly lower in the placebo group than the active implant. The histological inflammatory response to the TAF implant at 4 and 12 weeks in primates was graded as a severe reaction. Thus, while we were able to achieve sustained target dose we observed unacceptable inflammatory response locally at the implant tissue interface.

pharmacology and toxicology↗