ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry
| العنوان: | ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry |
|---|---|
| المؤلفون: | Jo Lynne Rokita, Brian J. Abraham, Shi Hao Tan, Mark W. Zimmerman, Richard A. Young, Nina Weichert-Leahey, Takaomi Sanda, Tze King Tan, Koshi Akahane, Lu Wang, Phuong Cao Thi Ngoc, Lee N. Lawton, John M. Maris, Adam D. Durbin, A. Thomas Look |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cellular differentiation, Science, Gene regulatory network, General Physics and Astronomy, Article, General Biochemistry, Genetics and Molecular Biology, Paediatric cancer, Neuroblastoma, 03 medical and health sciences, Adrenergic Agents, 0302 clinical medicine, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, medicine, Humans, Gene Regulatory Networks, lcsh:Science, neoplasms, Transcription factor, Regulation of gene expression, N-Myc Proto-Oncogene Protein, Multidisciplinary, biology, Proto-Oncogene Proteins c-ret, Cell Differentiation, Oncogenes, General Chemistry, LIM Domain Proteins, medicine.disease, Survival Analysis, Cell biology, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, ASCL1, 030104 developmental biology, Regulatory sequence, 030220 oncology & carcinogenesis, biology.protein, lcsh:Q, HAND2, Transcription, Transcription Factors |
| الوصف: | 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. Polymorphisms in LMO1 are associated with increased susceptibility to develop neuroblastoma. Here, the authors show that LMO1 directly induces the transcription factor ASCL1, which regulates the differentiation of neurons, demonstrating that ASCL1 is part of the adrenergic neuroblastoma core regulatory circuit. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f9a98ac92daa493e533708f8aaa6240 https://doaj.org/article/e6eb4888c5884e66bc019c078ad386b1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8f9a98ac92daa493e533708f8aaa6240 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
|---|