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

Autor: Lin Chen, Zhihui Luo, Chen Zhao, Qinglan Li, Yingjie Geng, Yong Xiao, Ming‐Kai Chen, Lianyun Li, Zhen‐Xia Chen, Min Wu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Advanced Science, Vol 9, Iss 23, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202200536
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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