ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry
Name
s41467-019-13515-5.pdf
Description
Published version
Size
3.34 MB
Format
Adobe PDF
Checksum (MD5)
916135fef325af0ae2dab8017f5be18b
Author(s)
Durbin, Adam D.
Abraham, Brian J.
Lawton, Lee N.
Young, Richard A.
Sanda, Takaomi
Date Issued
December 2019
Journal
Nature communications
Publisher
Springer Science and Business Media LLC
Citation
Wang, Lu et al. "ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry." Nature communications 10 (2019): 1039 © 2019 The Author(s)
Version
Final published version
Abstract
A heritable polymorphism within regulatory sequences of the LMO1 gene is associated with its elevated expression and increased susceptibility to develop neuroblastoma, but the oncogenic pathways downstream of the LMO1 transcriptional co-regulatory protein are unknown. Our ChIP-seq and RNA-seq analyses reveal that a key gene directly regulated by LMO1 and MYCN is ASCL1, which encodes a basic helix-loop-helix transcription factor. Regulatory elements controlling ASCL1 expression are bound by LMO1, MYCN and the transcription factors GATA3, HAND2, PHOX2B, TBX2 and ISL1—all members of the adrenergic (ADRN) neuroblastoma core regulatory circuitry (CRC). ASCL1 is required for neuroblastoma cell growth and arrest of differentiation. ASCL1 and LMO1 directly regulate the expression of CRC genes, indicating that ASCL1 is a member and LMO1 is a coregulator of the ADRN neuroblastoma CRC.
Subjects
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
General Chemistry
MIT Department
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41467-019-13515-5
