Abstract:
:Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type-specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics.
journal_name
Oncogenejournal_title
Oncogeneauthors
Chen Y,Xu L,Lin RY,Müschen M,Koeffler HPdoi
10.1038/s41388-020-01459-wsubject
Has Abstractpub_date
2020-10-01 00:00:00pages
6633-6646issue
43eissn
0950-9232issn
1476-5594pii
10.1038/s41388-020-01459-wjournal_volume
39pub_type
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