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Updated: Sep 5, 2025
Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq
Published on: April 19, 2013
Integrated analysis of genes encoding ATP-dependent chromatin remodellers identifies CHD7 as a potential target for
Xingyan Zhang1, Yaoyao Zhou2, Zhenyu Shi2
1The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
Background:
Genes participating in chromatin organization and regulation are frequently mutated or dysregulated in cancers. ATP-dependent chromatin remodelers (ATPCRs) play a key role in organizing genomic DNA within chromatin, therefore regulating gene expression. The oncogenic role of ATPCRs and the mechanism involved remains unclear.
Methods:
We analyzed the genomic and transcriptional aberrations of the genes encoding ATPCRs in The Cancer Genome Atlas (TCGA) cohort. A series of cellular experiments and mouse tumor-bearing experiments were conducted to reveal the regulatory function of CHD7 on the growth of colorectal cancer cells. RNA-seq and ATAC-seq approaches together with ChIP assays were performed to elucidate the downstream targets and the molecular mechanisms.
Results:
Our data showed that many ATPCRs represented a high frequency of somatic copy number alterations, widespread somatic mutations, remarkable expression abnormalities, and significant correlation with overall survival, suggesting several somatic driver candidates including chromodomain helicase DNA-binding protein 7 (CHD7) in colorectal cancer. We experimentally demonstrated that CHD7 promotes the growth of colorectal cancer cells in vitro and in vivo. CHD7 can bind to the promoters of target genes to maintain chromatin accessibility and facilitate transcription. We found that CHD7 knockdown downregulates AK4 expression and activates AMPK phosphorylation, thereby promoting the phosphorylation and stability of p53 and leading to the inhibition of the colorectal cancer growth. Our muti-omics analyses of ATPCRs across large-scale cancer specimens identified potential therapeutic targets and our experimental studies revealed a novel CHD7-AK4-AMPK-p53 axis that plays an oncogenic role in colorectal cancer.
Insights
Chromatin remodelers like CHD7 drive colorectal cancer growth by regulating gene expression. Targeting the CHD7-AK4-AMPK-p53 pathway may offer new therapeutic strategies for this cancer.
Area of Science:
- Cancer Genomics
- Epigenetics
- Molecular Oncology
Background:
- ATP-dependent chromatin remodelers (ATPCRs) are crucial for gene regulation and are frequently altered in cancer.
- The specific oncogenic roles and mechanisms of ATPCRs in cancer remain largely undefined.
- Chromatin organization genes are often dysregulated in various malignancies.
Purpose of the Study:
- To investigate the genomic and transcriptional landscape of ATPCRs in The Cancer Genome Atlas (TCGA) cohort.
- To elucidate the function and molecular mechanisms of chromodomain helicase DNA-binding protein 7 (CHD7) in colorectal cancer.
- To identify potential therapeutic targets within ATPCRs for colorectal cancer treatment.
Main Methods:
- Analysis of TCGA genomic and transcriptional data for ATPCRs.
- In vitro and in vivo experiments using colorectal cancer cell lines and mouse models.
- RNA-sequencing, ATAC-sequencing, and ChIP assays to determine downstream targets and mechanisms.
Main Results:
- Multiple ATPCRs, including CHD7, exhibit frequent alterations and correlate with survival in colorectal cancer.
- CHD7 promotes colorectal cancer cell proliferation in vitro and in vivo.
- A novel CHD7-AK4-AMPK-p53 signaling axis was identified, promoting colorectal cancer growth.
Conclusions:
- CHD7 acts as an oncogene in colorectal cancer by modulating chromatin accessibility and gene transcription.
- The identified CHD7-AK4-AMPK-p53 pathway represents a potential therapeutic vulnerability in colorectal cancer.
- Multi-omics analysis of ATPCRs reveals promising targets for cancer therapy.
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