Super-enhancer

In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity.[1][2][3] Because super-enhancers are frequently identified near genes important for controlling and defining cell identity, they may thus be used to quickly identify key nodes regulating cell identity.[3][4]

Enhancers have several quantifiable traits that have a range of values, and these traits are generally elevated at super-enhancers. Super-enhancers are bound by higher levels of transcription-regulating proteins and are associated with genes that are more highly expressed.[1][5][6][7] Expression of genes associated with super-enhancers is particularly sensitive to perturbations, which may facilitate cell state transitions or explain sensitivity of super-enhancer—associated genes to small molecules that target transcription.[1][5][6][8][9]

  1. ^ a b c Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA (April 2013). "Master transcription factors and mediator establish super-enhancers at key cell identity genes". Cell. 153 (2): 307–19. doi:10.1016/j.cell.2013.03.035. PMC 3653129. PMID 23582322.
  2. ^ Parker SC, Stitzel ML, Taylor DL, Orozco JM, Erdos MR, Akiyama JA, van Bueren KL, Chines PS, Narisu N, Black BL, Visel A, Pennacchio LA, Collins FS (October 2013). "Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants". Proceedings of the National Academy of Sciences of the United States of America. 110 (44): 17921–6. Bibcode:2013PNAS..11017921P. doi:10.1073/pnas.1317023110. PMC 3816444. PMID 24127591.
  3. ^ a b Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA (November 2013). "Super-enhancers in the control of cell identity and disease". Cell. 155 (4): 934–47. doi:10.1016/j.cell.2013.09.053. PMC 3841062. PMID 24119843.
  4. ^ Saint-André V, Federation AJ, Lin CY, Abraham BJ, Reddy J, Lee TI, Bradner JE, Young RA (March 2016). "Models of human core transcriptional regulatory circuitries". Genome Research. 26 (3): 385–96. doi:10.1101/gr.197590.115. PMC 4772020. PMID 26843070.
  5. ^ a b Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, et al. (July 2014). "Targeting transcription regulation in cancer with a covalent CDK7 inhibitor" (PDF). Nature. 511 (7511): 616–20. Bibcode:2014Natur.511..616K. doi:10.1038/nature13393. PMC 4244910. PMID 25043025.
  6. ^ a b Lovén J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA (April 2013). "Selective inhibition of tumor oncogenes by disruption of super-enhancers". Cell. 153 (2): 320–34. doi:10.1016/j.cell.2013.03.036. PMC 3760967. PMID 23582323.
  7. ^ Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ, Zhang LN, Weintraub AS, Schuijers J, Lee TI, Zhao K, Young RA (October 2014). "Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes". Cell. 159 (2): 374–87. doi:10.1016/j.cell.2014.09.030. PMC 4197132. PMID 25303531.
  8. ^ Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-Shahrour F, Zhang T, et al. (December 2014). "Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor". Cancer Cell. 26 (6): 909–22. doi:10.1016/j.ccell.2014.10.019. PMC 4261156. PMID 25490451.
  9. ^ Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, Abraham BJ, Sharma B, Yeung C, Altabef A, Perez-Atayde A, Wong KK, Yuan GC, Gray NS, Young RA, George RE (November 2014). "CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer". Cell. 159 (5): 1126–39. doi:10.1016/j.cell.2014.10.024. PMC 4243043. PMID 25416950.