WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013

Wang, Jing; Duncan, Dexter T.; Shi, Zhiao; Zhang, Bing

doi:10.1093/nar/gkt439

Cited by 1,436 publications

(1,273 citation statements)

References 26 publications

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“…A gene set of 158 AS genes (Fig. 2F, File S1) was analyzed with webgestalt (Zhang et al ., 2005; Wang et al ., 2013) and IPA (Ingenuity ® Systems, www.ingenuity.com). The most significant gene ontology (GO) biological processes enriched with AS genes were macromolecule metabolic processing and its subcategory RNA processing, including functions such as mRNA processing and RNA splicing (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

et al. 2015

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SummaryAlternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome‐wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild‐type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3–3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson–Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild‐type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.

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Section: Resultsmentioning

confidence: 99%

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

et al. 2015

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“…We used WebGestalt for Gene Ontology enrichment analyses (Wang et al , 2013). The lists of unique genes in gene symbol format were uploaded to WebGestalt and the GO Enrichment Analysis selected.…”

Section: Methodsmentioning

confidence: 99%

The landscape of human mutually exclusive splicing

Hatje

Rahman

Vidal

et al. 2017

Molecular Systems Biology

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Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA‐Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi‐cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila. Finally, MXEs are significantly enriched in pathogenic mutations and their spatio‐temporal expression might predict human disease pathology.

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“…Enriched motifs were identified via MEME-CHIP analysis of peak data using the MEME suite of tools (29). KEGG and Swiss-Prot/ UniProt keyword annotations were performed using the WebGestalt (30,31) and DAVID (32) bioinformatics analysis platforms.…”

Section: Methodsmentioning

confidence: 99%

MIST1 Links Secretion and Stress as both Target and Regulator of the Unfolded Protein Response

Hess

Strelau

Karki

et al. 2016

Molecular and Cellular Biology

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Transcriptional networks that govern secretory cell specialization, including instructing cells to develop a unique cytoarchitecture, amass extensive protein synthesis machinery, and be embodied to respond to endoplasmic reticulum (ER) stress, remain largely uncharacterized. In this study, we discovered that the secretory cell transcription factor MIST1 (Bhlha15), previously shown to be essential for cytoskeletal organization and secretory activity, also functions as a potent ER stress-inducible transcriptional regulator. Genome-wide DNA binding studies, coupled with genetic mouse models, revealed MIST1 gene targets that function along the entire breadth of the protein synthesis, processing, transport, and exocytosis networks. Additionally, key MIST1 targets are essential for alleviating ER stress in these highly specialized cells. Indeed, MIST1 functions as a coregulator of the unfolded protein response (UPR) master transcription factor XBP1 for a portion of target genes that contain adjacent MIST1 and XBP1 binding sites. Interestingly, Mist1 gene expression is induced during ER stress by XBP1, but as ER stress subsides, MIST1 serves as a feedback inhibitor, directly binding the Xbp1 promoter and repressing Xbp1 transcript production. Together, our findings provide a new paradigm for XBP1-dependent UPR regulation and position MIST1 as a potential biotherapeutic for numerous human diseases.

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WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013

Cited by 1,436 publications

References 26 publications

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

The landscape of human mutually exclusive splicing

MIST1 Links Secretion and Stress as both Target and Regulator of the Unfolded Protein Response

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