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.

Figure 1.

Interactive browsing in the dbCoRC. (A) Browse database for H1 human embryonic stem cells. Users can filter samples through species, biosample types, and tissue/cell types. A ‘Search’ box also enables fast fuzzy search. (B) Visualization of CRC model for H1 cells. (C) Exportable tabular information of core TFs in the H1 CRC model. (D) Potential downstream targets of NANOG within the H1 CRC model. (E) Interactive and exportable table showing the potential NANOG binding sites within the SE regions of core TFs in H1 cells. (F) Expression of NANOG mRNA across a panel of human cell lines.

Figure 2.

Searching in the dbCoRC and linking with external web servers for visualization. (A) Fuzzy search of NANOG and SOX2 in the database. (B) Results of search query from (A). (C) Visualization of the putative binding sites of core TFs across the extended SE region of NANOG via the UCSC genome browser.