Stimulation of interferon-β responses by aberrant SARS-CoV-2 small viral RNAs acting as retinoic acid-inducible gene-I agonists.

Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines. Despite this, the interferon (IFN) response is delayed, contributing to disease progression. Here, we report that SARS-CoV-2 excessively generates small viral RNAs (svRNAs) encoding exact 5' ends of positive-sense genes in human cells and , whereas endemic human coronaviruses (OC43 and 229E) produce significantly fewer similar svRNAs.

Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells.

Specific regulation of target genes by transforming growth factor-β (TGF-β) in a given cellular context is determined in part by transcription factors and cofactors that interact with the Smad complex. In this study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and we compared them with those in HaCaT epidermal keratinocytes to elucidate the mechanisms of cell type- and context-dependent regulation of transcription induced by TGF-β. Our results show that 81% of the Smad2/3 binding regions in HepG2 cells were not shared with those found in HaCaT cells.

Genome-wide profiling of the core clock protein BMAL1 targets reveals a strict relationship with metabolism.

Circadian rhythms are common to most organisms and govern much of homeostasis and physiology. Since a significant fraction of the mammalian genome is controlled by the clock machinery, understanding the genome-wide signaling and epigenetic basis of circadian gene expression is essential. BMAL1 is a critical circadian transcription factor that regulates genes via E-box elements in their promoters.

Promoter-wide analysis of Smad4 binding sites in human epithelial cells.

Smad4, the common partner Smad, is a key molecule in transforming growth factor-beta (TGF-beta) family signaling. Loss of Smad4 expression is found in several types of cancer, including pancreatic cancer and colon cancer, and is related to carcinogenesis. Here we identified Smad4 binding sites in the promoter regions of over 25 500 known genes by chromatin immunoprecipitation on a microarray (ChIP-chip) in HaCaT human keratinocytes.

PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt.

p53 And Akt are critical players regulating tumorigenesis with opposite effects: whereas p53 transactivates target genes to exert its function as a tumor suppressor, Akt phosphorylates its substrates and transduces downstream survival signals. In addition, p53 and Akt negatively regulate each other to balance survival and death signals within a cell. We now identify PHLDA3 as a p53 target gene that encodes a PH domain-only protein.

Allelic imbalances and homozygous deletion on 8p23.2 for stepwise progression of hepatocarcinogenesis.

Unlabelled: Early hepatocellular carcinoma (eHCC) originates from the hepatocytes of chronic liver disease and develops into classical hepatocellular carcinoma (HCC). To identify sequential genetic changes in multistep hepatocarcinogenesis, we analyzed molecular karyotypes using oligonucleotide genotyping 50K arrays. First, 1q21.

Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factor beta signaling.

The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor beta (TGF-beta) signaling from the plasma membrane to the nucleus. Many transcription factors have been shown to cooperate with the Smad2/3 proteins in regulating the transcription of target genes, enabling appropriate gene expression by cells. Here we identified 1,787 Smad2/3 binding sites in the promoter regions of over 25,500 genes by chromatin immunoprecipitation on microarray in HaCaT keratinocytes.

Distinct chromosomal bias of gene expression signatures in the progression of hepatocellular carcinoma.

To identify the chromosomal aberrations associated with the progression of liver cancer, we applied expression imbalance map analysis to gene expression data from 31 hepatocellular carcinomas and 19 noncancerous tissues. Expression imbalance map analysis, which detects mRNA expression imbalance correlated with chromosomal regions, showed that expression gains of 1q21-23 (74%), 8q13-21 (48%), 12q23-24 (41%), 17q12-21(48%), 17q25 (25%), and 20q11 (22%) and losses of 4q13 (48%), 8p12-21 (32%), 13q14 (32%), and 17p13 (29%) were significantly associated with hepatocellular carcinoma. Most regions with altered expression identified by expression imbalance map were also identified in previous reports using comparative genomic hybridization.