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k/vol1/fastq/SRR157/050/SRR15712250/SRR15712250_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/074/SRR15712274/SRR15712274_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/069/SRR15712269/SRR15712269_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/059/SRR15712259/SRR15712259_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/060/SRR15712260/SRR15712260_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/062/SRR15712262/SRR15712262_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/057/SRR15712257/SRR15712257_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/051/SRR15712251/SRR15712251_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/045/SRR15712245/SRR15712245_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/041/SRR15712241/SRR15712241_1.fastq.gzprimaryOK200GenomicsHideo Watanabe, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinaihttps://www.ebi.ac.uk/ena/browser/view/PRJNA760440Homo sapiensMolecular classification of small cell lung cancer (SCLC), a lethal and heterogeneous disease, was recently proposed based on expression of four lineage-defining transcription factors SCLC-A (ASCL1), SCLC-N (NEUROD1), SCLC-Y (YAP1), and SCLC-P (POU2F3). In this study, unsupervised clustering of genome-wide histone H3K27 acetylation profiles uncovered previously unappreciated epigenomic heterogeneity of this recalcitrant disease. Specifically, the major SCLC-A subtype, which accounts for approximately 70% of all SCLC cases, was subdivided into two new subtypes SCLC-A1 and SCLC-A2. SCLC-A1 is distinguished by the presence of super-enhancer at the NKX2-1 locus, also observed in a murine SCLC model and human SCLC specimens. We found NKX2-1, a master regulator of lung lineages as well as a critical lineage factor in central nervous system, is uniquely functionally relevant in SCLC-A1, where it maintains neural lineage rather than pulmonary epithelial identity. Through integrative proteomic, transcriptomic and cistromic analyses, we found that maintenance of this neural identity in SCLC-A1 is mediated by collaborative transcriptional activity with another neuronal transcriptional factor SOX1 Overall design: Genome-wide profiles of histone H3K27 acetylation in SCLC cell lines.xref:PubMed:35848993ENAfalseTranscriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (ChIP-Seq K27ac)Transcriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (ChIP-Seq K27ac)2025-09-242022-10-07PRJNA760440GSE183362960635848993