Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-019-13515-5
Title: ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry
Authors: Wang, Lu 
Tan, Tze King 
Durbin, Adam D
Zimmerman, Mark W
Abraham, Brian J
Tan, Shi Hao 
Ngoc, Phuong Cao Thi 
Weichert-Leahey, Nina
Akahane, Koshi
Lawton, Lee N
Rokita, Jo Lynne
Maris, John M
Young, Richard A
Look, A Thomas
Sanda, Takaomi 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ACHAETE-SCUTE HOMOLOG-1
UP-REGULATION
TAL1 COMPLEX
ENHANCER
TRANSCRIPTION
PROTEINS
MUTATION
DRIVES
TARGET
RET
Issue Date: 9-Dec-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Wang, Lu, Tan, Tze King, Durbin, Adam D, Zimmerman, Mark W, Abraham, Brian J, Tan, Shi Hao, Ngoc, Phuong Cao Thi, Weichert-Leahey, Nina, Akahane, Koshi, Lawton, Lee N, Rokita, Jo Lynne, Maris, John M, Young, Richard A, Look, A Thomas, Sanda, Takaomi (2019-12-09). ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry. NATURE COMMUNICATIONS 10 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-019-13515-5
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.
Source Title: NATURE COMMUNICATIONS
URI: https://scholarbank.nus.edu.sg/handle/10635/205902
ISSN: 20411723
DOI: 10.1038/s41467-019-13515-5
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