dbSUPER: a database of super-enhancers in mouse and human genome

Super-enhancers are clusters of transcriptional enhancers that drive cell-type-specific gene expression and are crucial to cell identity. Many disease-associated sequence variations are enriched in super-enhancer regions of disease-relevant cell types. Thus, super-enhancers can be used as potential biomarkers for disease diagnosis and therapeutics. Current studies have identified super-enhancers in more than 100 cell types and demonstrated their functional importance. However, a centralized resource to integrate all these findings is not currently available. We developed dbSUPER (http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing. The data can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for downstream analysis, and can also be visualized in the UCSC genome browser where custom tracks can be added automatically. The data can be downloaded and exported in variety of formats. Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions. We believe dbSUPER is a valuable resource for the biology and genetic research communities.

[1]  David Haussler,et al.  The UCSC genome browser and associated tools , 2012, Briefings Bioinform..

[2]  Charles Y. Lin,et al.  Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. , 2013, Cancer cell.

[3]  Melissa J. Landrum,et al.  RefSeq: an update on mammalian reference sequences , 2013, Nucleic Acids Res..

[4]  Hong Zhang,et al.  Inhibition of Bromodomain Proteins for the Treatment of Human Diffuse Large B-cell Lymphoma , 2014, Clinical Cancer Research.

[5]  David A. Orlando,et al.  Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes , 2013, Cell.

[6]  J. Banerji,et al.  Expression of a β-globin gene is enhanced by remote SV40 DNA sequences , 1981, Cell.

[7]  B. L,et al.  The accessible chromatin landscape of the human genome , 2016 .

[8]  Britta A. M. Bouwman,et al.  A Single Oncogenic Enhancer Rearrangement Causes Concomitant EVI1 and GATA2 Deregulation in Leukemia , 2014, Cell.

[9]  Nathan C. Sheffield,et al.  The accessible chromatin landscape of the human genome , 2012, Nature.

[10]  Stephen C. J. Parker,et al.  Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants , 2013, Proceedings of the National Academy of Sciences.

[11]  Jon C. Aster,et al.  NOTCH1–RBPJ complexes drive target gene expression through dynamic interactions with superenhancers , 2013, Proceedings of the National Academy of Sciences.

[12]  Paulo P. Amaral,et al.  Molecular Cell Previews RePlace Your BETs : The Dynamics of Super Enhancers , 2014 .

[13]  G. Bejerano,et al.  Enhancers: five essential questions , 2013, Nature Reviews Genetics.

[14]  Ryan A. Flynn,et al.  A unique chromatin signature uncovers early developmental enhancers in humans , 2011, Nature.

[15]  V. Corces,et al.  Enhancer function: new insights into the regulation of tissue-specific gene expression , 2011, Nature Reviews Genetics.

[16]  Anton Nekrutenko,et al.  Integrating diverse databases into an unified analysis framework: a Galaxy approach , 2011, Database J. Biol. Databases Curation.

[17]  R. Young,et al.  Super-Enhancers in the Control of Cell Identity and Disease , 2013, Cell.

[18]  Yan Liu,et al.  Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. , 2014, Cancer cell.

[19]  Tatiana A. Tatusova,et al.  Entrez Gene: gene-centered information at NCBI , 2004, Nucleic Acids Res..

[20]  Aaron R. Quinlan,et al.  Bioinformatics Applications Note Genome Analysis Bedtools: a Flexible Suite of Utilities for Comparing Genomic Features , 2022 .

[21]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[22]  R. Young,et al.  Histone H3K27ac separates active from poised enhancers and predicts developmental state , 2010, Proceedings of the National Academy of Sciences.

[23]  A. Stark,et al.  Transcriptional enhancers: from properties to genome-wide predictions , 2014, Nature Reviews Genetics.

[24]  Timothy J. Durham,et al.  Systematic analysis of chromatin state dynamics in nine human cell types , 2011, Nature.

[25]  The Uniprot Consortium,et al.  UniProt: a hub for protein information , 2014, Nucleic Acids Res..

[26]  K. Zhao,et al.  Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization , 2012, Cell Research.

[27]  Tsviya Olender,et al.  GeneCards Version 3: the human gene integrator , 2010, Database J. Biol. Databases Curation.

[28]  D. MacPherson,et al.  Treating transcriptional addiction in small cell lung cancer. , 2014, Cancer cell.

[29]  James E. Bradner,et al.  Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability , 2014, Cell.

[30]  R. Young,et al.  An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element , 2014, Science.

[31]  Jussi Taipale,et al.  Cancer by super-enhancer , 2014, Science.

[32]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[33]  Adelina Rogowska-Wrzesinska,et al.  Transcription factor cooperativity in early adipogenic hotspots and super-enhancers. , 2014, Cell reports.

[34]  María Martín,et al.  UniProt: A hub for protein information , 2015 .

[35]  Yijun Ruan,et al.  B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity , 2014, Cell.

[36]  Sridhar Ramaswamy,et al.  Targeting transcription regulation in cancer with a covalent CDK7 inhibitor , 2014, Nature.

[37]  Laurie A Boyer,et al.  Distal enhancers: new insights into heart development and disease. , 2014, Trends in cell biology.

[38]  David A. Orlando,et al.  Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers , 2013, Cell.

[39]  Jesse R. Dixon,et al.  Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions , 2012, Nature.

[40]  A. Dean,et al.  Enhancer function: mechanistic and genome-wide insights come together. , 2014, Molecular cell.

[41]  Andrew L. Kung,et al.  NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis. , 2014, Molecular cell.

[42]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[43]  A. Visel,et al.  ChIP-seq accurately predicts tissue-specific activity of enhancers , 2009, Nature.

[44]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[45]  Bing Ren,et al.  CRISPR Reveals a Distal Super-Enhancer Required for Sox2 Expression in Mouse Embryonic Stem Cells , 2014, PloS one.

[46]  D. Karolchik,et al.  The UCSC Genome Browser database: 2016 update , 2015, bioRxiv.

[47]  Robert Tjian,et al.  Looping Back to Leap Forward: Transcription Enters a New Era , 2014, Cell.

[48]  Clifford A. Meyer,et al.  Cistrome: an integrative platform for transcriptional regulation studies , 2011, Genome Biology.

[49]  Charles Y. Lin,et al.  Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. , 2015, Molecular cell.

[50]  Timothy J. Durham,et al.  "Systematic" , 1966, Comput. J..

[51]  Cory Y. McLean,et al.  GREAT improves functional interpretation of cis-regulatory regions , 2010, Nature Biotechnology.

[52]  B. Ren,et al.  Mapping Human Epigenomes , 2013, Cell.

[53]  F. Grosveld,et al.  Enhancers and silencers: an integrated and simple model for their function , 2012, Epigenetics & Chromatin.

[54]  Stephen C. J. Parker,et al.  Stretch-Enhancers Delineate Disease-Associated Regulatory Nodes in T Cells , 2014, Nature.

[55]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[56]  J. Lieb,et al.  What are super-enhancers? , 2014, Nature Genetics.