The SMYD family proteins in immunology

Basic Research ◽

Host Immunity ◽

Biological Processes ◽

Pathogen Infection ◽

Macrophage Function ◽

Epigenetics is an emerging field, due to its relevance in the regulation of a wide range of biological processes. The Su(Var)3-9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing (SMYD) proteins, named SMYD1, SMYD2, SMYD3, SMYD4 and SMYD5, are enzymes that catalyse methylation of histone and non-histone substrates, thereby playing a key role in gene expression regulation in many biological contexts, such as muscle development and physiology, haematopoiesis and many types of cancer. This review focuses on a relatively unexplored aspect of SMYD family members - their relation with immunology. Here, immunology is defined in the broadest sense of the word, including basic research on macrophage function or host immunity against pathogen infection, as well as clinical studies, most of which are centred on blood cancers.

GEREDB: Gene expression regulation database curated by mining abstracts from literature

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720019500240 ◽

2019 ◽

Vol 17 (04) ◽

pp. 1950024 ◽

Cited By ~ 2

Author(s):

Tinghua Huang ◽

Xiali Huang ◽

Bomei Shi ◽

Min Yao

Keyword(s):

Gene Expression ◽

Gene Expression Data ◽

Biological Database ◽

Biological Processes ◽

Expression Data ◽

Biological Responses ◽

Human Genes ◽

The Relationship ◽

Made In

Understanding how genes are expressed and regulated in different biological processes are fundamental and challenging issues. Considerable progress has been made in studying the relationship between the expression and regulation of human genes. However, it is difficult to use these resources productively to analyze gene expression data. GEREDB ( www.thua45.cn/geredb ) has been developed to facilitate analyses that will provide insights into the regulation of genes that govern specific biological responses. GEREDB is a publicly available, manually curated biological database that stores the data regarding relationships between expression and regulation of human genes. To date, more than 39,000 Links have been contextually annotated by reviewing more than 53,000 abstracts. GEREDB can be searched using the official NCBI gene symbol as a query, and it can be downloaded along with the GEREA software package. GEREDB has the ability to analyze user-supplied gene expression data in a causal analysis oriented manner using the GEREA bioinformatics tool.

Overlapping and Unique Roles for C-Terminal Binding Protein 1 (CtBP1) and CtBP2 during Mouse Development

Molecular and Cellular Biology ◽

10.1128/mcb.22.15.5296-5307.2002 ◽

2002 ◽

Vol 22 (15) ◽

pp. 5296-5307 ◽

Cited By ~ 199

Author(s):

Jeffrey D. Hildebrand ◽

Philippe Soriano

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Genetic Interaction ◽

Binding Protein ◽

Biological Processes ◽

Vertebrate Development ◽

Mouse Development ◽

Axial Patterning ◽

ABSTRACT The C-terminal binding protein (CtBP) family of proteins has been linked to multiple biological processes through their association with numerous transcription factors. We generated mice harboring mutations in both Ctbp1 and Ctbp2 to address the in vivo function of CtBPs during vertebrate development. Ctbp1 mutant mice are small but viable and fertile, whereas Ctbp2-null mice show defects in axial patterning and die by E10.5 due to aberrant extraembryonic development. Mice harboring various combinations of Ctbp1 and Ctbp2 mutant alleles exhibit dosage-sensitive defects in a wide range of developmental processes. The strong genetic interaction, as well as transcription assays with CtBP-deficient cells, indicates that CtBPs have overlapping roles in regulating gene expression. We suggest that the observed phenotypes reflect the large number of transcription factors whose activities are compromised in the absence of CtBP.

hTFtarget: a comprehensive database for regulations of human transcription factors and their targets

10.1101/843656 ◽

2019 ◽

Cited By ~ 1

Author(s):

Qiong Zhang

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Dna Sequences ◽

Chromatin Immunoprecipitation ◽

Target Genes ◽

Epigenetic Modification ◽

Wide Range ◽

Chromatin Immunoprecipitation Sequencing ◽

User Friendly

Transcription factors (TFs) as key regulators play crucial roles in biological processes. The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression. The accumulated data of Chromatin immunoprecipitation sequencing (ChIP-Seq) provides great opportunities to discover the TF-target regulations across different conditions. In this study, we constructed a database named hTFtarget, which integrated huge human TF target resources (7,190 ChIP-Seq samples of 659 TFs and high confident TF binding sites of 699 TFs) and epigenetic modification information to predict accurate TF-target regulations. hTFtarget offers the following functions for users to explore TF-target regulations: 1) Browse or search general targets of a query TF across datasets; 2) Browse TF-target regulations for a query TF in a specific dataset or tissue; 3) Search potential TFs for a given target gene or ncRNA; 4) Investigate co-association between TFs in cell lines; 5) Explore potential co-regulations for given target genes or TFs; 6) Predict candidate TFBSs on given DNA sequences; 7) View ChIP-Seq peaks for different TFs and conditions in genome browser. hTFtarget provides a comprehensive, reliable and user-friendly resource for exploring human TF-target regulations, which will be very useful for a wide range of users in the TF and gene expression regulation community. hTFtarget is available at http://bioinfo.life.hust.edu.cn/hTFtarget.

86 Extensive FAP expression analysis in 23 tumor indications and potential application in defining the patient population in FAP-targeting cancer immunotherapies

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.086 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A94-A94

Author(s):

Sebastian Dziadek ◽

Anton Kraxner ◽

Wei-Yi Cheng ◽

Mike Flores ◽

Noah Theiss ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Clinical Studies ◽

Islet Cells ◽

Phase 1 ◽

Clinical Trial Data ◽

Progression Free Survival ◽

Metastatic Tumor ◽

Intensity Level ◽

BackgroundFibroblast activation protein alpha (FAP) is frequently over-expressed in the tumor microenvironment (TME) while exhibiting limited expression in normal tissues. FAP expression was reported to be immunosuppressive in tumor mouse models and generally associated with worse prognosis in clinical studies. Therefore, it is important to understand the context in which FAP both exhibits immunosuppressive characteristics and be a useful target for immunotherapy.MethodsComprehensive immunohistochemistry (IHC) analyses on formalin-fixed paraffin-embedded tissue specimens with emphasis on lymph nodes and primary and metastatic tumor lesions spanning a wide range of indications were undertaken in this study. FAP staining of tumor tissues was performed with an optimized IHC robust-prototype-assay (RPA) and manually scored. The area (normal stroma & neoplastic) staining positively relative to the total tumor area at each intensity level was recorded and an H-score calculated (FAP-intensity score).These were supplemented by gene expression analysis using public as well as Roche phase 1, 2 and 3 cancer immunotherapy (CIT) clinical trial data sets.ResultsAnalysing FAP expression on normal tissue confirmed the general absence of FAP apart from a subset of pancreatic islet cells. Unlike the more homogenous expression of typical protein targets on tumor cells, FAP expression in the TME is heterogeneous in both pattern and intensity, requiring the analysis of a large sample set. Therefore, we evaluated 1216 samples from 23 tumor indications and 70 sub-indications. FAP expression exhibited a significant spread ranging from indications with highly abundant expression to those with low coverage.Using data from matching IHC and gene expression samples we confirmed FAP mRNA expression to significantly correlate with RPA H-scores (Spearman correlation: 0.62) (N=289, P=1.2E-31). Gene expression data from 12 atezolizumab clinical studies, including standard of care (SOC) randomized studies, with more than 6000 samples from 4 major indications were interrogated for the association between FAP expression and clinical response as evaluated by overall and progression free survival. This analysis suggests that FAP expression is generally associated with higher hazard ratios across all atezolizumab-treated samples (OS: 95% CI 1.04–1.09; PFS: 1.04–1.08), with the highest effect observed in Renal Cell Carcinoma (OS: 95% CI 1.08–1.31; PFS: 1.05–1.21), indicating a potential role of FAP in limiting CIT.ConclusionsData from these analyses can tailor indication and patient enrichment strategies for achieving optimal FAP-targeting. We propose to select indications with FAP-levels that are high enough to enable drug accumulation, yet low enough to reduce immunosuppressive effects that can hamper successful immunotherapy.

Distinct transcriptional profiles in plasma exosomes associated with recurrence of nasopharyngeal carcinoma patients with standard treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6534 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6534-6534

Author(s):

Yongjiang Li ◽

Xue Zheng ◽

Xiaoqi Xie ◽

Yukai Hu ◽

Jingbo Kang ◽

...

Keyword(s):

Gene Expression ◽

Nasopharyngeal Carcinoma ◽

Survival Data ◽

Standard Treatment ◽

Expression Profiles ◽

Endoplasmic Reticulum Membrane ◽

Rna Expression ◽

Biological Processes ◽

Cox Regression Analysis ◽

6534 Background: Nasopharyngeal carcinoma (NPC) is endemic with a high prevalence in Southern China, Asia,cetuximab and North Africa. Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. In the progression of NPC, the tumor cells constantly release exosomes into the surrounding environment and also into the circulating blood. The aim of this study was to explore the association between RNA expression in plasma exosomes and prognosis of NPC patients after standard treatment. Methods: In this retrospective study, a total of 25 eligible NPC patients were included: 12 patients in the recurrence (R) subgroup and 13 patients in the no recurrence (NR) subgroup. RNA was extracted from the exosomes of plasma specimens which were collected at West China Hospital, Sichuan University. Gene expression profiles were conducted by using the RNA-sequencing platform. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between R and NR subgroups. The gene set variance analysis (GSVA) was performed to explore C5 gene sets enrichment related to the recurrence after standard treatment. Results: We observed 332 DEGs between R and NR subgroups, which include 125 up-regulated and 207 down-regulated genes (R vs. NR,∣log2fold change∣>1, p<0.05). Moreover, hierarchical clustering analysis of the 332 DEGs revealed that all samples clustered into two subgroups, with cluster 1 containing 82% (9/11) recurrence patients and cluster 2 containing 79% (11/14) no recurrence patients. Further, univariate Cox regression analysis showed that 293 out of 332 DEGs were significantly correlated with DFS ( p<0.05), such as TRAM1, CAPN1, SAT1 and ACTB. GSVA and Log Rank test of survival data demonstrated that a total of 824 pathways/biological processes were significantly different between R andNR subgroups ( p<0.05). Specifically, the top 9 pathways/biological processes, such lipoxygenase pathway, rough endoplasmic reticulum membrane and low density lipoprotein particle clearance, was mainly enriched in the NR subgroup ( p <0.001). Conclusions: Profiling of plasma exosomes RNA in NPC patients reveals distinctive gene expression pattern between patients with or without recurrence. Further functional analysis revealed that top enriched 9 pathways/biological processes may correlate with a favorable prognosis and are worth investigating. Moreover, for the prognosis of patients with NPC, RNA expression of plasma exosomes may be a potentially valuable research object.

First Analyses of Lysine Succinylation Proteome and Overlap between Succinylation and Acetylation in Solenopsis Invicta Buren (Hymenoptera: Formicidae)

10.21203/rs.3.rs-953231/v1 ◽

2021 ◽

Author(s):

Jingwen Ye ◽

Jun Li

Keyword(s):

Solenopsis Invicta ◽

Basic Research ◽

Invasive Pest ◽

Biological Processes ◽

Atpase Subunit ◽

Post Translational Modifications ◽

Lysine Succinylation ◽

Starting Point ◽

Wide Range ◽

Solenopsis Invicta Buren

Abstract Background: Lysine succinylation (Ksu) exists in both eukaryotes and prokaryotes, and influences a variety of metabolism processes. However, little attention has been paid to Ksu in insects, especially the notorious invasive pest Solenopsis invicta. Results: In this study, the first analyses of Ksu proteome and overlap between Ksu and lysine acetylation (Kac) in S. invicta were presented. 3,753 succinylated sites in 893 succinylated proteins were tested. The dihydrolipoyl dehydrogenase, V-type proton ATPase subunit G, and tubulin alpha chain all had evolutionary conservatism among diverse ant or bee species. Immunoblotting validation showed that there were many Ksu protein bands with a wide range of molecular mass. In addition, 1,230 sites in 439 proteins were highly overlapped between Ksu and Kac. 54.05% of Ksu proteins in cytoplasm were acetylated. The results demonstrated that Ksu may play a vital part in the allergization, redox metabolism, sugar, fat, and protein metabolism, energy production, immune response, and biosynthesis of various secondary metabolites.Conclusions: Ksu and Kac were two ubiquitous protein post-translational modifications participated in a variety of biological processes. Our results may supply rich resources and a starting point for the molecular basic research of regulation on metabolic pathways and other biological processes by succinylation and acetylation.

Programmable RNA recognition using a CRISPR-associated Argonaute

10.1101/208041 ◽

2017 ◽

Cited By ~ 1

Author(s):

Audrone Lapinaite ◽

Jennifer A. Doudna ◽

Jamie H. D. Cate

Keyword(s):

Gene Expression ◽

Complex Mixture ◽

Seed Region ◽

Single Nucleotide ◽

Guide Rna ◽

Argonaute Proteins ◽

Wide Range ◽

Domains Of Life

ABSTRACTArgonaute proteins (Agos) are present in all domains of life. While the physiological function of eukaryotic Agos in regulating gene expression is well documented, the biological roles of many of their prokaryotic counterparts remain enigmatic. In some bacteria, Agos are associated with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci and use non-canonical 5’-hydroxyled guide RNAs (gRNAs) for nucleic acid targeting. Here we show that using 5-bromo-2′-deoxyuridine (BrdU) as the 5’ nucleotide of gRNAs stabilizes in vitro reconstituted CRISPR-associated Marinitoga piezophila Argonaute-gRNA complexes (MpAgo RNPs) and significantly improves their specificity and affinity for RNA targets. Using reconstituted MpAgo RNPs with 5’-BrdU modified gRNAs, we mapped the seed region of the gRNA, and identified the nucleotides of the gRNA that play the most significant role in targeting specificity. We also show that these MpAgo RNPs can be programmed to distinguish between substrates that differ by a single nucleotide, using permutations at the 6th and 7th positions in the gRNA. Using these specificity features, we employed MpAgo RNPs to detect specific Adenosine to Inosine edited RNAs in a complex mixture. These findings broaden our mechanistic understanding of the interactions of Argonautes with guide and substrate RNAs, and demonstrate that MpAgo RNPs with 5’-BrdU modified gRNAs can be used as a highly-specific RNA-targeting platform to probe RNA biology.SIGNIFICANCEArgonaute proteins are present in bacteria, archaea and eukaryotes. They play an important role in a wide range of biological processes, from transcriptional and translational gene expression regulation to defense against viruses and silencing of mobile genetic elements. Here we present mechanistic insights into the interactions of the CRISPR-associated Marinitoga piezophila Argonaute (MpAgo) with its guide RNA (gRNA) and RNA substrates. By modifying the 5’-nucleotide of the gRNA, we demonstrate that MpAgo-gRNA complexes (RNPs) are easily programmable, have high affinity to fully complementary RNA substrates, and can discriminate by over 300 fold between substrates that differ by only a single nucleotide. These MpAgo RNPs should be useful for probing endogenous RNAs in living cells.

Inheritance of gene expression throughout fruit development in chili pepper

Scientific Reports ◽

10.1038/s41598-021-02151-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Christian Escoto-Sandoval ◽

Neftalí Ochoa-Alejo ◽

Octavio Martínez

Keyword(s):

Gene Expression ◽

Fruit Development ◽

R Package ◽

Chili Pepper ◽

Wild Accession ◽

Biological Processes ◽

Genome Wide ◽

Cell Components

AbstractGene expression is the primary molecular phenotype and can be estimated in specific organs or tissues at particular times. Here we analyzed genome-wide inheritance of gene expression in fruits of chili pepper (Capsicum annuum L.) in reciprocal crosses between a domesticated and a wild accession, estimating this parameter during fruit development. We defined a general hierarchical schema to classify gene expression inheritance which can be employed for any quantitative trait. We found that inheritance of gene expression is affected by both, the time of fruit development as well as the direction of the cross, and propose that such variations could be common in many developmental processes. We conclude that classification of inheritance patterns is important to have a better understanding of the mechanisms underlying gene expression regulation, and demonstrate that sets of genes with specific inheritance pattern at particular times of fruit development are enriched in different biological processes, molecular functions and cell components. All curated data and functions for analysis and visualization are publicly available as an R package.

Viral vectors as a novel tool for clinical and neuropsychiatric research applications

General Psychiatry ◽

10.1136/gpsych-2018-000015 ◽

2018 ◽

Vol 31 (2) ◽

pp. e000015 ◽

Cited By ~ 4

Author(s):

Yao Wang ◽

Zhiwei Hu ◽

Peijun Ju ◽

Shan Yin ◽

Fujie Wang ◽

...

Keyword(s):

Gene Expression ◽

Viral Vectors ◽

Molecular Mechanisms ◽

Viral Vector ◽

Neurological Diseases ◽

Basic Research ◽

Research Field ◽

Research Fields ◽

Pathogenic Genes

BackgroundA viral vector is a genetically modified vector produced by genetic engineering. As pathogenic genes in the virus are completely or largely eliminated, it is safe to be widely used in multidisciplinary research fields for expressing genes, such as neuroscience, metabolism, oncology and so on. Neuroscience and psychiatry are the most closely related disciplines in either basic research or clinical research, but the application of viral vectors in neuropsychiatry has not received much attention or not been widely accepted.ObjectiveThis article will focus on the application of viral vectors in basic and clinical neuropsychiatric research.MethodsBy using viral vectors, scientists can perform neurological labelling, gene expression regulation and physiological manipulation for investigating phenomenon from molecular mechanisms to behaviours. At the same time, to treat mental or neurological disorders, viral vectors can be designed for gene therapy, which alter gene expression levels or repair mutated genes in the brains of patients.PerspectiveViral vectors play an important role in basic research and clinical applications. To further understand brain function and prevent mental and neurological diseases, we hypothesize that viral vectors could be used along with various advanced technologies, such as sequencing and high-throughput expression analysis in the neuroscience research field.

Plant Long Noncoding RNAs: New Players in the Field of Post-Transcriptional Regulations

Non-Coding RNA ◽

10.3390/ncrna7010012 ◽

2021 ◽

Vol 7 (1) ◽

pp. 12

Author(s):

Camille Fonouni-Farde ◽

Federico Ariel ◽

Martin Crespi

Keyword(s):

Gene Expression ◽

Cellular Localization ◽

Molecular Mechanisms ◽

Large Fraction ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Genomic Research ◽

Protein Coding ◽

The first reference to the “C-value paradox” reported an apparent imbalance between organismal genome size and morphological complexity. Since then, next-generation sequencing has revolutionized genomic research and revealed that eukaryotic transcriptomes contain a large fraction of non-protein-coding components. Eukaryotic genomes are pervasively transcribed and noncoding regions give rise to a plethora of noncoding RNAs with undeniable biological functions. Among them, long noncoding RNAs (lncRNAs) seem to represent a new layer of gene expression regulation, participating in a wide range of molecular mechanisms at the transcriptional and post-transcriptional levels. In addition to their role in epigenetic regulation, plant lncRNAs have been associated with the degradation of complementary RNAs, the regulation of alternative splicing, protein sub-cellular localization, the promotion of translation and protein post-translational modifications. In this review, we report and integrate numerous and complex mechanisms through which long noncoding transcripts regulate post-transcriptional gene expression in plants.