MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia

Nicholas T. Crump (), Alastair L. Smith, Laura Godfrey, Ana M. Dopico-Fernandez, Nicholas Denny, Joe R. Harman, Joseph C. Hamley, Nicole E. Jackson, Catherine Chahrour, Simone Riva, Siobhan Rice, Jaehoon Kim, Venkatesha Basrur, Damian Fermin, Kojo Elenitoba-Johnson, Robert G. Roeder, C. David Allis, Irene Roberts, Anindita Roy, Huimin Geng, James O. J. Davies and Thomas A. Milne ()
Additional contact information
Nicholas T. Crump: University of Oxford
Alastair L. Smith: University of Oxford
Laura Godfrey: University of Oxford
Ana M. Dopico-Fernandez: University of Oxford
Nicholas Denny: University of Oxford
Joe R. Harman: University of Oxford
Joseph C. Hamley: University of Oxford
Nicole E. Jackson: University of Oxford
Catherine Chahrour: University of Oxford
Simone Riva: University of Oxford
Siobhan Rice: University of Oxford
Jaehoon Kim: Korea Advanced Institute of Science and Technology
Venkatesha Basrur: University of Michigan
Damian Fermin: University of Michigan
Kojo Elenitoba-Johnson: University of Pennsylvania
Robert G. Roeder: The Rockefeller University
C. David Allis: The Rockefeller University
Irene Roberts: University of Oxford
Anindita Roy: University of Oxford
Huimin Geng: University of California, San Francisco, San Francisco
James O. J. Davies: University of Oxford
Thomas A. Milne: University of Oxford

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40981-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40981-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40981-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().