WashU Epigenome Browser update 2022

Li, Daofeng; Purushotham, Deepak; Harrison, Jessica K.; Hsu, Silas; Zhuo, Xiaoyu; Fan, Changxu; Liu, Shane; Xu, Vincent; Chen, Samuel; Xu, Jason; Ouyang, Shinyi; Wu, Angela S; Wang, Ting

doi:10.1093/nar/gkac238

Cited by 78 publications

(74 citation statements)

References 26 publications

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“…To annotate Bach2 motifs in DARs, we downloaded the Bach2 motif (MA1101.1) from the JASPAR ( Castro-Mondragon et al, 2022 ) motif database, and used FIMO (v5.4.1) ( Grant et al, 2011 ) to scan DARs for the presence of this motif with a p-value cutoff at 0.0005. ATAC signal was visualized using WashU Epigenome Browser ( Li et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

Li¹,

Bern²,

Miao³

et al. 2022

eLife

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BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD27+CD11b+ cells and decreased upon further maturation. Bach2 showed an organ and tissue-specific expression pattern in NK cells. Bach2 expression positively correlated with the expression of transcription factor TCF1 and negatively correlated with genes encoding NK effector molecules and those involved in the cell cycle. Lack of Bach2 expression caused changes in chromatin accessibility of corresponding genes. In the end, Bach2-deficiency resulted in increased proportions of terminally differentiated NK cells with increased production of granzymes and cytokines. NK cell-mediated control of tumor metastasis was also augmented in the absence of Bach2. Therefore, Bach2 is a key checkpoint protein regulating NK terminal maturation.

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Section: Methodsmentioning

confidence: 99%

The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

Li¹,

Bern²,

Miao³

et al. 2022

eLife

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“…Chromatin histone marks for the region were extracted from the ENCODE GM12878 cell line track and visualized using the WASHU genome browser [ 25 ]. We also extracted chromatin conformation data from a promoter capture HiC (PCHiC) study [ 26 ] to determine possible regional chromatin interactions between SNP-containing regions and neighboring genes.…”

Section: Methodsmentioning

confidence: 99%

Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1

Fazel-Najafabadi

Rallabandi

Singh

et al. 2022

Genes

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Genome-wide association studies have identified 2p13.1 as a prominent susceptibility locus for systemic lupus erythematosus (SLE)—a complex, multisystem autoimmune disease. However, the identity of underlying causal variant (s) and molecular mechanisms for increasing disease susceptibility are poorly understood. Using meta-analysis (cases = 10,252, controls = 21,604) followed by conditional analysis, bioinformatic annotation, and eQTL and 3D-chromatin interaction analyses, we computationally prioritized potential functional variants and subsequently experimentally validated their effects. Ethnicity-specific meta-analysis revealed striking allele frequency differences between Asian and European ancestries, but with similar odds ratios. We identified 20 genome-wide significant (p < 5 × 10−8) variants, and conditional analysis pinpointed two potential functional variants, rs6705628 and rs2272165, likely to explain the association. The two SNPs are near DGUOK, mitochondrial deoxyguanosine kinase, and its associated antisense RNA DGUOK-AS1. Using luciferase reporter gene assays, we found significant cell type- and allele-specific promoter activity at rs6705628 and enhancer activity at rs2272165. This is supported by ChIP-qPCR showing allele-specific binding with three histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), transcriptional coactivator p300, CCCTC-binding factor (CTCF), and transcription factor ARID3A. Transcriptome data across 28 immune cell types from Asians showed both SNPs are cell-type-specific but only in B-cells. Splicing QTLs showed strong regulation of DGUOK-AS1. Genotype-specific DGOUK protein levels are supported by Western blots. Promoter capture Hi-C data revealed long-range chromatin interactions between rs2272165 and several nearby promoters, including DGUOK. Taken together, we provide mechanistic insights into how two noncoding variants underlie SLE risk at the 2p13.1 locus.

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“…The Encode (https://www.encodeproject.org/; accessed on 10 September 2019) database was used to analyze the binding of SPI1 to the MNDA promoter and visualized with the WashU Epigenome Browser online tool (http://epigenomegateway.wustl.edu/browser/; accessed on 10 September 2019) [19,20].…”

Section: Tf Chip-seq Analysis Of Spi1 Binding To the Mnda Promotermentioning

confidence: 99%

Abnormal Gene Expression Regulation Mechanism of Myeloid Cell Nuclear Differentiation Antigen in Lung Adenocarcinoma

Tang

Wang

Bajinka

et al. 2022

Biology

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Lung adenocarcinoma (LA) is the main pathological type of lung cancer with a very low 5-year survival rate. In the present study, after downloading the mRNA, miRNA, and DNA methylation sequencing data from TCGA, combined with the downloaded clinical data, comparative analysis, prognostic analysis, GO and KEGG analysis, GSEA analysis, methylation analysis, transcriptional regulation and post-transcriptional regulation were performed. We found that both methylation and gene expression of MNDA in LA were down-regulated, while high expression of MNDA was associated with good overall survival in LA. To probe the mechanism, further analysis showed that SPI1 was the main transcription factor of MNDA, but it was also down-regulated in LA. At the same time, the expression of eight target miRNAs of MNDA was significantly up-regulated, and the expression of hsa-miR-33a-5p and hsa-miR-33b-5p were verified to directly target MNDA. In conclusion, the abnormal expression of MNDA in LA is the result of the combined effects of transcriptional and post-transcriptional regulation.

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WashU Epigenome Browser update 2022

Cited by 78 publications

References 26 publications

The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1

Abnormal Gene Expression Regulation Mechanism of Myeloid Cell Nuclear Differentiation Antigen in Lung Adenocarcinoma

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