small molecule Chip-seq

PURPOSE: Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is the target of the small molecules lenalidomide (Len) and avadomide (Ava). Upon binding of the drugs, Aiolos and Ikaros are recruited to the E3 ligase, ubiquitylated and subsequently degraded. In DLBCL cells, Aiolos and Ikaros are direct transcriptional repressors of interferon stimulated genes (ISG) and degradation of these substrates results in increased ISG protein levels resulting in decreased proliferation and apoptosis...

Osteosarcoma (OS) is the most common primary malignant bone tumor in canines and humans. However, there have been no new successful therapies that improve long-term survival in several decades. This indicates the need for novel therapeutic targets for treating OS. Core binding factor is a heterodimeric transcriptional complex, comprised of proteins runt-related transcription factor 2 (RUNX2) and core-binding factor subunit Beta (CBFβ), that promotes transcription of genes related to bone formation, osteoblast differentiation, and bone mineralization...

There is an evolving threat to our healthcare system-the rise of antibiotic-resistant bacteria, such as Acinetobacter baumannii, and the depletion of our few useful antibiotics. These bacteria have developed an ability to fight off increasing numbers of antibiotics used to treat hospitalized patients. To combat these infections, new solutions must be discovered to target the bacteria's ability to resist drugs and restore the efficacy of our arsenal of antibiotics. One possible therapeutic target is the BfmRS two-protein signaling system, which activates many genes that determine antibiotic resistance and virulence in A...

Diffuse Large B Cell Lymphoma (DLBCL) accounts for 40% of Non-Hodgkin-Lymphoma, and 30% to 40% of patients will succumb to relapsed/refractory disease (rrDLBCL). Patients with rrDLBCL generally have low long-term survival rates due to a lack of efficient salvage therapies. Small molecule inhibitors targeting the histone methyltransferase EZH2 represent an emerging group of novel therapeutics that show promising clinical efficacy in patients with rrDLBCL. The mechanisms that control acquired resistance to this class of targeted therapies, however, remain poorly understood...

Small noncoding RNAs (snRNA) have been emerging as promising diagnostic biomarkers for detecting early stage cancer. Currently existing methods for snRNA detection, including northern blot, reverse transcription-polymerase chain reaction, microarrays and RNA-Seq, are limited to time-consuming, low sensitivity, expensive instrumentation or complex analysis of data. Herein, we present a rapid quantitative analysis of multiple liver cancer-associated exosomal snRNA by a nucleic acid toehold probe-based photonic resonator absorption microscopy (PRAM) assay, with digital resolution and high sensitivity...

Monoubiquitination plays a critical role as one of the largest histone post-translational modifications (PTMs). Recent study has revealed that histone H2B monoubiquitination (H2Bub1) at a unique lysine 120 (K120) is widely involved in the development of inflammation progression. However, small-molecules directly targeting H2B to exert anti-inflammation effects via editing monoubiquitination have not been hitherto reported. In this study, we first discover a natural small-molecule epoxymicheliolide (ECL), which directly binds to H2B to inhibit microglia-mediated neuroinflammation in vitro and in vivo...

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+ (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+ iOPCs was similar to that of O4+ OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes...

Objective: Septic shock is the severe complication of sepsis, with a high mortality. The inflammatory response regulates the immune status and mediates the progression of septic shock. In this study, we aim to identify the key immune-related genes (IRGs) of septic shock and explore their potential mechanism. Methods: Gene expression profiles of septic shock blood samples and normal whole blood samples were retrieved from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression Portal (GTEx). The differential expression genes (DEGs) and septic shock-specific immune-related genes (SSSIRGs) were evaluated and identified, along with the immune components by "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT, version x)" algorithm...

Background: Spinal cord injury (SCI) is a severe neurological deficit affecting both young and older people worldwide. The potential role of key enhancer RNAs (eRNAs) in SCI remains elusive, which is a prominent challenge in the trauma repair process. This study aims to investigate the roles of key eRNAs, transcription factors (TFs), signaling pathways, and small-molecule inhibitors in SCI using multi-omics bioinformatics analysis. Methods: Microarray data of peripheral blood mononuclear cell (PBMC) samples from 27 healthy volunteers and 25 chronic-phase SCI patients were retrieved from the Gene Expression Omnibus database...

BACKGROUND: Long non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes glioma progression. METHODS: RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays, and a mouse xenograft model were performed to determine the functions of TMEM44-AS1...

The three-dimensional organization of chromatin and its time-dependent changes greatly affect virtually every cellular function, especially DNA replication, genome maintenance, transcription regulation, and cell differentiation. Sequencing-based techniques such as ChIP-seq, ATAC-seq, and Hi-C provide abundant information on how genomic elements are coupled with regulatory proteins and functionally organized into hierarchical domains through their interactions. However, visualizing the time-dependent changes of such organization in individual cells remains challenging...

Transcriptional regulators that integrate cellular and environmental signals to control cell division are well known in bacteria and eukaryotes, but their existence is poorly understood in archaea. We identified a conserved gene ( cdrS ) that encodes a small protein and is highly transcribed in the model archaeon Haloferax volcanii. The cdrS gene could not be deleted, but CRISPR interference (CRISPRi)-mediated repression of the cdrS gene caused slow growth and cell division defects and changed the expression of multiple genes and their products associated with cell division, protein degradation, and metabolism...

Neointimal hyperplasia after vascular injury is a representative complication of restenosis. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is involved in the pathogenesis of vascular intimal hyperplasia. PARP16, a member of the poly(ADP-ribose) polymerases family, is correlated with the nuclear envelope and the ER. Here, we found that PERK and IRE1 α are ADP-ribosylated by PARP16, and this might promote proliferation and migration of smooth muscle cells (SMCs) during the platelet-derived growth factor (PDGF)-BB stimulating...

RNA-binding protein PSF functions as an epigenetic modifier by interacting with long noncoding RNAs and the corepressor complex. PSF also promotes RNA splicing events to enhance oncogenic signals. In this study, we conducted an in vitro chemical array screen and identified multiple small molecules that interact with PSF. Several molecules inhibited RNA binding by PSF and decreased prostate cancer cell viability. Among these molecules and its derivatives was a promising molecule, No. 10-3 [7,8-dihydroxy-4-(4-methoxyphenyl)chromen-2-one], that was the most effective at blocking PSF RNA-binding ability and suppressing treatment-resistant prostate and breast cancer cell proliferation...

ParABS, the most widespread bacterial DNA segregation system, is composed of a centromeric sequence, parS, and two proteins, the ParA ATPase and the ParB DNA binding proteins. Hundreds of ParB proteins assemble dynamically to form nucleoprotein parS-anchored complexes that serve as substrates for ParA molecules to catalyze positioning and segregation events. The exact nature of this ParBS complex has remained elusive, what we address here by revisiting the Stochastic Binding model (SBM) introduced to explain the non-specific binding profile of ParB in the vicinity of parS...

BACKGROUND: Invasion and metastasis of cervical cancer are the main factors affecting the prognosis of patients with cervical squamous cell carcinoma (CESC). Therefore, it is of vital importance to find novel biomarkers that are associated with CESC invasion and metastasis, which will aid in the amelioration of individualized therapeutic methods for advanced patients. METHODS: The gene expression profiles of 10 metastatic and 116 non-metastatic samples were downloaded from The Cancer Genome Atlas (TCGA), where differentially expressed genes (DEGs) were defined...

Rationale: Osteosarcoma (OS), the most common type of bone tumor, which seriously affects the patients' limb function and life quality. OS has a strong tendency of lung metastasis, and the five-year survival rate of patients with metastatic osteosarcoma is less than 20%. Thus, new treatment targets and strategies are urgently needed. Methods: The expression of the histone demethylase KDM6B and H3K27me3 levels in OS specimens were analyzed using quantitative PCR and immunohistochemical assays. The biological functions of KDM6B were determined using in vitro transwell, wound healing assays, and an in vivo orthotopic injection-induced lung metastasis model...

HLA-C arose during evolution of pregnancy in the great apes 10 to 15 million years ago. It has a dual function on placental extravillous trophoblasts (EVTs) as it contributes to both tolerance and immunity at the maternal-fetal interface. The mode of its regulation is of considerable interest in connection with the biology of pregnancy and pregnancy abnormalities. First-trimester primary EVTs in which HLA-C is highly expressed, as well as JEG3, an EVT model cell line, were employed. Single-cell RNA-seq data and quantitative PCR identified high expression of the transcription factor ELF3 in those cells...

Nonalcoholic-fatty-liver-disease (NAFLD) is the result of imbalances in hepatic lipid partitioning and is linked to dietary factors. We demonstrate that conjugated linoleic acid (CLA) when given to mice as a dietary supplement, induced an enlarged liver, hepatic steatosis, and increased plasma levels of fatty acid (FA), alanine transaminase, and triglycerides. The progression of NAFLD and insulin resistance was reversed by GW6471 a small-molecule antagonist of peroxisome proliferator-activated receptor α (PPARα)...

Tumor-initiating cells (TICs) maintain heterogeneity within tumors and seed metastases at distant sites, contributing to therapeutic resistance and disease recurrence. In colorectal cancer (CRC), strategy that effectively eradicates TICs and is of potential value for clinical use still remains in need. Methods : The anti-tumorigenic activity of a small-molecule inhibitor of KDM6 histone demethylases named GSK-J4 in CRC was evaluated by in vitro assays and in vivo imaging of xenografted tumors. Sphere formation, flow cytometry analysis of cell surface markers and intestinal organoid formation were performed to examine the impact of GSK-J4 on TIC properties...