Biology subjects

Su, D.

Publications and source records attributed to Su, D..

41 records · Page 3Linked to original sources

bioRxiv2019

The usage of six human IGHJ genes follows a particular nonrandom selection: The recombination signal sequence affects the usage frequency of six human IGHJ genes

The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the \"12/23\" rule and the \"beyond 12/23\" rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10%[~]20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether physiological or various pathological conditions. Furthermore, analysis of the recombination signal sequences suggested that the conserved nonamer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this \"background repertoire\", we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response.

genomics↗

bioRxiv2019

C17orf53 defines a novel pathway involved in inter-strand crosslink repair

ATR kinase is a master regulator of genome maintenance and participates in DNA replication and various DNA repair pathways. In a genome-wide screening for ATR-dependent fitness genes, we identified a previously uncharacterized gene, C17orf53, whose loss led to hypersensitivity to ATR inhibition. C17orf53 is conserved in vertebrate and is required for efficient cell proliferation. Loss of C17orf53 slowed down DNA replication and led to pronounced ICL repair defect. Further genetic analyses revealed that C17orf53 functions downstream in ICL repair pathway, probably by affecting the loading of repair factors such as RAD54. In addition, we showed that C17orf53 is a ssDNA- and RPA-binding protein, both of which are important for its functions in the cell. Taken together, C17orf53 is a novel component involved in ICL repair pathway.

biochemistry↗

bioRxiv2019

Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics is one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs as like atorvastatin (ATO) both in effectiveness and the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on gut microbiota. Hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, both on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (TNF-, IL-1{beta}, CRP), with strain JQII-5 most significant. Besides, these effects were associated with restoration of the microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genus and reversed genus was found to be correlated to inflammatory state and serum lipid level. Compared with ATO, probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.

microbiology↗

bioRxiv2019

Bimodal Regulation of the PRC2 Complex by USP7 Underlies Melanomagenesis

Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in melanoma cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation. Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives melanoma cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during melanoma progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of melanoma patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for melanoma.

cell biology↗

bioRxiv2018

The heparin-binding proteome in normal pancreas and murine experimental acute pancreatitis

Acute pancreatitis (AP) is acute inflammation of the pancreas, mainly caused by gallstones and alcohol, driven by changes in communication between cells. Heparin-binding proteins (HBPs) play a central role in health and diseases. Therefore, we used heparin affinity proteomics to identify extracellular HBPs in pancreas and plasma of normal mice and in a caerulein mouse model of AP. Many new extracellular HBPs (360) were discovered in the pancreas, taking the total number of HBPs known to 786. Extracellular pancreas HBPs form highly interconnected protein-protein interaction networks in both normal pancreas (NP) and AP. Thus, HBPs represent an important set of extracellular proteins with significant regulatory potential in the pancreas. HBPs in NP are associated with biological functions such as molecular transport and cellular movement that underlie pancreatic homeostasis. However, in AP HBPs are associated with additional inflammatory processes such as acute phase response signalling, complement activation and mitochondrial dysfunction, which has a central role in the development of AP. Plasma HBPs in AP included known AP biomarkers such as serum amyloid A, as well as emerging targets such as histone H2A. Other HBPs such as alpha 2-HS glycoprotein (AHSG) and histidine-rich glycoprotein (HRG) need further investigation for potential applications in the management of AP. Pancreas HBPs are extracellular and so easily accessible and are potential drug targets in AP, whereas plasma HBPs represent potential biomarkers for AP. Thus, their identification paves the way to determine which HBPs may have potential applications in the management of AP.

biochemistry↗