dbCoRC: a database of core transcriptional regulatory circuitries modeled by H3K27ac ChIP-seq signals

Abstract Core transcription regulatory circuitry (CRC) is comprised of a small group of self-regulated transcription factors (TFs) and their interconnected regulatory loops. Studies from embryonic stem cells and other cellular models have revealed the elementary roles of CRCs in transcriptional control of cell identity and cellular fate. Systematic identification and subsequent archiving of CRCs across diverse cell types and tissues are needed to explore both cell/tissue type-specific and disease-associated transcriptional networks. Here, we present a comprehensive and interactive database (dbCoRC, http://dbcorc.cam-su.org) of CRC models which are computationally inferred from mapping of super-enhancer and prediction of TF binding sites. The current version of dbCoRC contains CRC models for 188 human and 50 murine cell lines/tissue samples. In companion with CRC models, this database also provides: (i) super enhancer, typical enhancer, and H3K27ac landscape for individual samples, (ii) putative binding sites of each core TF across the super-enhancer regions within CRC and (iii) expression of each core TF in normal or cancer cells/tissues. The dbCoRC will serve as a valuable resource for the scientific community to explore transcriptional control and regulatory circuitries in biological processes related to, but not limited to lineage specification, tissue homeostasis and tumorigenesis.

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

[2]  Alexander E. Kel,et al.  TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes , 2005, Nucleic Acids Res..

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

[4]  Ernest Fraenkel,et al.  Core transcriptional regulatory circuitry in human hepatocytes , 2006, Molecular systems biology.

[5]  Vladimir B. Bajic,et al.  TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins , 2010, Nucleic Acids Res..

[6]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[7]  Megan F. Cole,et al.  Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells , 2008, Cell.

[8]  R. Wilson,et al.  The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis , 2017, Neuron.

[9]  Xi Chen,et al.  Reciprocal Transcriptional Regulation of Pou5f1 and Sox2 via the Oct4/Sox2 Complex in Embryonic Stem Cells , 2005, Molecular and Cellular Biology.

[10]  R. Young,et al.  Transcriptional Regulation and Its Misregulation in Disease , 2013, Cell.

[11]  Yu Xue,et al.  AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors , 2014, Nucleic Acids Res..

[12]  S. Orkin,et al.  An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells , 2008, Cell.

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

[14]  Christopher J. Ott,et al.  BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. , 2017, Molecular cell.

[15]  Tatiana A. Tatusova,et al.  Gene: a gene-centered information resource at NCBI , 2014, Nucleic Acids Res..

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

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

[18]  M. Ferrer,et al.  PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability. , 2017, Cancer discovery.

[19]  Roland Eils,et al.  Active medulloblastoma enhancers reveal subgroup-specific cellular origins , 2016, Nature.

[20]  Aziz Khan,et al.  dbSUPER: a database of super-enhancers in mouse and human genome , 2015, bioRxiv.

[21]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[22]  Fabien C. Lamaze,et al.  FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells , 2016, Scientific Reports.

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

[24]  Ning Hou,et al.  RhesusBase: a knowledgebase for the monkey research community , 2012, Nucleic Acids Res..

[25]  David Haussler,et al.  The UCSC Genome Browser database: 2017 update , 2016, Nucleic Acids Res..

[26]  R. Lovell-Badge,et al.  Multipotent cell lineages in early mouse development depend on SOX2 function. , 2003, Genes & development.

[27]  Nuno A. Fonseca,et al.  Expression Atlas update—a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments , 2013, Nucleic Acids Res..

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

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

[30]  William Stafford Noble,et al.  FIMO: scanning for occurrences of a given motif , 2011, Bioinform..

[31]  R. Hoffmann.  A wiki for the life sciences where authorship matters , 2008, Nature Genetics.

[32]  T. Mikkelsen,et al.  The NIH Roadmap Epigenomics Mapping Consortium , 2010, Nature Biotechnology.

[33]  Natalia B. Ivanova,et al.  Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. , 2012, Cell stem cell.

[34]  Richard A Young,et al.  Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. , 2012, Cancer cell.

[35]  Gerald A. Higgins,et al.  Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury , 2017, Pharmaceutical Research.

[36]  Shane J. Neph,et al.  Circuitry and Dynamics of Human Transcription Factor Regulatory Networks , 2012, Cell.

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

[38]  T. Enver,et al.  Forcing cells to change lineages , 2009, Nature.

[39]  Dan M. Bolser,et al.  Ensembl Genomes 2016: more genomes, more complexity , 2015, Nucleic Acids Res..

[40]  Sarah A. Teichmann,et al.  Genomic repertoires of DNA-binding transcription factors across the tree of life , 2010, Nucleic acids research.

[41]  X. Chen,et al.  The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells , 2006, Nature Genetics.

[42]  Richard A Young,et al.  Models of human core transcriptional regulatory circuitries , 2016, Genome research.

[43]  Mikael Bodén,et al.  MEME Suite: tools for motif discovery and searching , 2009, Nucleic Acids Res..

[44]  Bin Zhang,et al.  SEA: a super-enhancer archive , 2015, Nucleic Acids Res..

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