Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis‐Associated Colorectal Cancer

• Published in: Advanced science Vol. 9; no. 23; pp. e2200536 - n/a
• Main Authors: Chen, Lin, Luo, Zhihui, Zhao, Chen, Li, Qinglan, Geng, Yingjie, Xiao, Yong, Chen, Ming‐Kai, Li, Lianyun, Chen, Zhen‐Xia, Wu, Min
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.08.2022; John Wiley and Sons Inc; Wiley
• Subjects: chromatin states; colitis‐associated cancer; Colorectal cancer; DNA methylation; Epigenetics; Gene expression; Genomes; histone modification; Inflammation; Inflammatory bowel disease; NF‐κB, OTX2; Patients; Software; Transcription factors
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202200536

Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, the mechanisms for transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory factors for colitis‐associated cancer. Here, a systematic epigenomic study of histone modifications is performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM‐DSS‐induced CRC mouse model. In combination with transcriptomic data, the authors generate a dataset of 105 deep sequencing files and illustrate the dynamic landscape of chromatin states at five time points during inflammation‐cancer transition. Functional gene clusters are identified based on dynamic transcriptomic and epigenomic information, and key signaling pathways in the process are illustrated. This study's results reveal that enhancer state regions play important roles during inflammation‐cancer transition. It predicts novel transcription factors based on enhancer information, and experimentally proves OTX2 as a critical tumor suppressive transcription factor. Taken together, this study provides comprehensive epigenomic data and reveals novel molecular mechanisms for colitis‐associated cancer. The dynamic changes of chromatin states during the transition from inflammation to cancer are studied in a colitis‐associated cancer model. Multiple omics analysis reveal that enhancer state regions play important roles during inflammation‐cancer transition. Novel transcription factors, such as OTX2, are discovered as critical factors for colorectal cancer.