Abstract
A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the “SE active core TFs analysis” and “TF enrichment analysis” tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.
Highlights
Transcription factors (TFs) regulate gene expression by binding to specific DNA sequences [1]
The construction of the Cancer CRC platform was based on the comprehensive identification and analysis of CRCs from various cancer types
We found that transcription factors (TFs) with higher frequencies tended to have higher degree, and these two properties of core TFs could help select TFs that are important in cancers
Summary
Transcription factors (TFs) regulate gene expression by binding to specific DNA sequences [1]. A small number of TFs that are expressed in each cell type control the gene expression programs in specific cells, and dysregulation of these genes can cause various diseases [2,3,4,5,6] These TF clusters play crucial roles in the pathology and development of cancers. These TFs are essential for the proliferation of undifferentiated ESCs and contribute to the pluripotency and self-renewal of stem cells [9,10,11,12] Together, these TFs cooperate to regulate cellular gene expression by binding regulatory elements that impact expressed genes. Identification of CRCs in various cancers is essential for a better understanding of cell/tissue characteristics and for addressing fundamental molecular and cellular biological questions
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