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Series GSE69394 Query DataSets for GSE69394
Status Public on Jul 21, 2016
Title Distinct Function for ASCL1 and NEUROD1 in Pulmonary Neuroendocrine Tumors (ChIP-seq)
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are high-grade pulmonary neuroendocrine tumors. The neural basic helix-loop-helix (bHLH) transcription factors ASCL1 and NEUROD1 have been shown to play crucial roles in promoting the malignant behavior and survival of human SCLC cell lines. In this study, we find ASCL1 and NEUROD1 identify distinct neuroendocrine tumors, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1 and NEUROD1 are often bound in super-enhancers that are associated with highly expressed genes in their respective SCLC cell lines suggesting different cell lineage of origin for these tumors. ASCL1 targets oncogenic genes such as MYCL1, RET, and NFIB, while NEUROD1 targets the oncogenic gene MYC. Although ASCL1 and NEUROD1 regulate different genes, many of these gene targets commonly contribute to neuroendocrine and cell migration function. ASCL1 in particular also regulates genes in the NOTCH pathway and genes important in cell-cycle dynamics. Finally, we demonstrate ASCL1 but not NEUROD1 is required for SCLC and LCNEC tumor formation in current in vivo genetic mouse models of pulmonary neuroendocrine tumors
Overall design ChIP-seq analysis performed on three ASCL1high and two NEUROD1high human SCLC cell lines to identify ASCL1 and/or NEUROD1 binding sites in these two types of cells. Also, we performed ChIP-seq for Ascl1 binding sites in mouse neuroendocrine lung tumors obtained from Trp53;Rb1;Rbl2 triple knockout model mice treated with Adeno-CMVCRE intratracheally.
Contributor(s) Borromeo MD, Savage TK, Kollipara RK, He M, Augustyn A, Osborne JK, Girard L, Minna JD, Gazdar AF, Cobb MH, Johnson JE
Citation(s) 27452466
Submission date May 29, 2015
Last update date May 15, 2019
Contact name Jane E Johnson
Organization name UT Southwestern Medical Center
Department Neuroscience
Street address 5323 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390-9111
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (9)
GSM1700637 Human SCLC H128 ASCL1 ChIP
GSM1700638 Human SCLC H2107 ASCL1 ChIP
GSM1700639 Human SCLC H889 ASCL1 ChIP
This SubSeries is part of SuperSeries:
GSE69398 Distinct Function for ASCL1 and NEUROD1 in Pulmonary Neuroendocrine Tumors
BioProject PRJNA285364
SRA SRP058872

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE69394_RAW.tar 475.8 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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