Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a...

Area of Science:

• Epigenetics
• Molecular Biology
• Cancer Research

Background:

• Epigenetic alterations, including chromatin modifications like H3K4me3 and H3K9ac, are crucial in colon cancer development.
• These modifications can lead to genomic instability and dysregulate gene expression, impacting oncogenic pathways.

Purpose of the Study:

• To investigate early, pre-tumorigenic epigenetic events driving colorectal cancer (CRC).
• To integrate genome-wide epigenetic data with RNA expression profiles in a rat model of colon cancer progression.

Main Methods:

• Utilized high-throughput sequencing for RNA, H3K4me3, and H3K9ac.
• Compared differentially expressed transcripts (DE) and differentially enriched regions (DER) in an in-vivo rat colon cancer model.
• Analyzed carcinogen (AOM) effects on genome-wide epigenetic and transcriptomic landscapes.

Main Results:

• Carcinogen exposure induced genome-wide changes in RNA (116 DE genes), H3K9ac (49 DERs), and H3K4me3 (7678 DERs).
• Interferon-associated innate immune responses were impacted at the RNA level.
• Extensive H3K4me3 alterations were linked to colon tumorigenesis, but not yet reflected in RNA expression during early progression.

Conclusions:

• Carcinogen-induced H3K4me3 changes serve as early indicators of future transcriptional events in colon cancer.
• Epigenetic modifications precede detectable RNA expression changes in early colorectal cancer progression.
• Understanding these early epigenetic events is key to deciphering malignant transformation.