Core transcriptional regulatory circuitries in cancer.

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

Oncogene

journal_title

Oncogene

authors

Chen Y,Xu L,Lin RY,Müschen M,Koeffler HP

doi

10.1038/s41388-020-01459-w

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

6633-6646

issue

43

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-01459-w

journal_volume

39

pub_type

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