Dynamic properties of enhancer and promoter during DNA damage in hepatocellular carcinoma

Area of Science:

• Genomics
• Cancer Biology
• Molecular Biology

Background:

• DNA damage is a key driver of cancer development.
• Understanding the dynamic multi-omics changes in regulatory elements during the DNA damage response (DDR) is crucial but limited, especially in hepatocellular carcinoma (HCC).

Purpose of the Study:

• To investigate the dynamic changes in multi-omics signatures of enhancers and promoters during the DDR in HCC.
• To understand how pre-damage regulatory element states influence responses to DNA damage.
• To identify transcription factors (TFs) involved in the DDR and their differential activity in regulatory elements.

Main Methods:

• Analysis of multi-omics data (expression levels, chromatin accessibility, element activity) for enhancers and promoters at different stages of DNA damage in HCC.
• Comparative analysis of regulatory element behavior before and after DNA damage.
• Identification and activity assessment of transcription factors, including p53, in response to DNA damage.

Main Results:

• Enhancers and promoters show dynamic similarity and duality in expression, accessibility, and activity during DNA damage in HCC.
• The accessibility and activity of regulatory elements prior to DNA damage significantly influence their post-damage regulatory characteristics.
• Transcription factor activity, particularly p53 binding, differs between enhancers and promoters during the DDR.

Conclusions:

• The study reveals complex, dynamic changes in cis-regulatory elements during the DDR in HCC.
• Pre-damage states are critical determinants of regulatory element function following DNA damage.
• Differential TF activity, like p53, in enhancers versus promoters highlights intricate DDR mechanisms.