Biology subjects

Ryu, J.

Publications and source records attributed to Ryu, J..

2 recordsLinked to original sources

bioRxiv2019

An insect serotonin receptor mediates cellular immune responses and its inhibition by phenylethylamide derivatives from bacterial secondary metabolites

Serotonin (5-hydroxytryptamine: 5-HT) is a biogenic monoamine that mediates immune responses and modulates nerve signal in insects. Se-5HTR, a specific receptor of serotonin, has been identified in the beet armyworm, Spodoptera exigua. It is classified into subtype 7 among known 5HTRs. Se-5HTR was expressed in all developmental stages of S. exigua. It was expressed in all tested tissues of larval stage. Its expression was up-regulated in hemocytes and fat body in response to immune challenge. RNA interference (RNAi) of Se-5HTR exhibited significant immunosuppression by preventing cellular immune responses such as phagocytosis and nodulation. Treatment with an inhibitor (SB-269970) specific to 5HTR subtype 7 resulted in significant immunosuppression. Such immunosuppression was also induced by bacterial secondary metabolites derived from Xenorhabdus and Photorhabdus. To determine specific bacterial metabolites inhibiting Se-5HTR, this study screened 37 bacterial secondary metabolites with respect to cellular immune responses associated with Se-5HTR and selected 10 potent inhibitors. These 10 selected compounds competitively inhibited cellular immune responses against 5-HT and shared phenylethylamide (PEA) chemical skeleton. Subsequently, 46 PEA derivatives were screened and resulting potent chemicals were used to design a compound to be highly inhibitory against Se-5HTR. The designed compound was chemically synthesized. It showed high immunosuppressive activities along with specific and competitive inhibition activity for Se-5HTR. This study reports the first 5HT receptor from S. exigua and provides its specific inhibitor designed from bacterial metabolites and their derivatives. Author SummarySerotonin (5-hydroxytryptamine: 5-HT) plays a crucial role in mediating nerve and immune signals in insects. Interruption of 5-HT signal leads to malfunctioning of various insect physiological processes. Se-5HTR, a 5-HT receptor of beet armyworm, Spodoptera exigua, was identified and classified as subtype 7 (5-HT7) of 5-HT receptors. A specific inhibitor (SB-269970) for 5-HT7 highly inhibited immune responses such as phagocytosis and nodulation mediated by Se-5HTR. Two entomopathogenic bacteria, Xenorhabdus and Photorhabdus, could secrete potent inhibitors against immune responses mediated by 5-HTR. Bacterial secondary metabolites were screened against Se-5HTR-mediating immune responses. Most of resulting compounds shared phenylethylamide (PEA) chemical skeleton. Subsequent screening using PEA derivatives supported the importance of this chemical skeleton. Based on their relative inhibitory activities, a compound was designed and synthesized. This novel compound possessed high inhibitory activities against Se-5HTR-mediating immune responses and exhibited competitive inhibition with 5-HT.

immunology↗

bioRxiv2018

A new class of constitutively active super-enhancers is associated with fast recovery of 3D chromatin loops

Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation. In this study, through a comprehensive analysis of super-enhancers in 30 human cell/tissue types, we identified a new class of super-enhancers which are constitutively active across most cell/tissue types. These common super-enhancers are associated with universally highly expressed genes in contrast to the canonical definition of super-enhancers that assert cell-type specific gene regulation. In addition, the genome sequence of these super-enhancers is highly conserved by evolution and among humans, advocating their universal function in genome regulation. Integrative analysis of 3D chromatin loops demonstrates that, in comparison to the cell-type specific super-enhancers, the cell-type common super-enhancers present a striking association with rapidly recovering loops. We propose that a new class of super-enhancers may play an important role in the early establishment of 3D chromatin structure.\n\nBackgroundSuper-enhancers or stretch enhancers are defined by a strong enrichment of mediators and transcription-regulating proteins, appearing to play a deterministic role in cellular identity by controlling the expression of cell-type specific genes[1, 2]. Previous studies have revealed the critical function of super-enhancers during development and differentiation[3]. The enrichment of disease-associated single nucleotide polymorphism (SNP) in super-enhancers compared to that of typical enhancers proposed a substantial link between super-enhancers and many complex human diseases[2]. In addition, a set of recent studies have proposed potential functions of super-enhancers in the extremely long-range chromatin communications and the establishment of 3D chromatin loops[4]. These results suggest a more universal role of super-enhancers in genome regulation apart from cell-type specific gene regulation, but little is known about the mechanisms underlying these various functions. To extend the current knowledge of super-enhancers and their biological roles, we conducted a comprehensive analysis of super-enhancer activities across 30 human cell/tissue types. Our analysis suggests that a substantial number of super-enhancers exhibits prevalent activities across cell-types in terms of H3K27ac signals, and that these non-canonical super-enhancers are involved in the formation of fast recovering chromatin loops.\n\nNoteA genome browser session has been set up for visualization of the super-enhancer domains described in the current study- https://genome.ucsc.edu/cgi-bin/hgTracks?hgS-doOtherUser=submit&hgS-otherUserName=abundantiavosliberabit&hgS-otherUserSessionName=SuperEnhancerDomain

genomics↗