Emerging Approaches to Profile Accessible Chromatin from Formalin-Fixed Paraffin-Embedded Sections

Area of Science:

• Genomics
• Epigenetics
• Molecular Biology

Background:

• Nucleosome distribution dictates gene activity, with open chromatin linked to active promoters and enhancers.
• Chromatin accessibility patterns are vital for understanding normal development and disease progression.
• High-throughput sequencing methods like DNase-seq and ATAC-seq identify open chromatin, but face challenges with FFPE tissues.

Purpose of the Study:

• To review common methods for mapping open chromatin regions.
• To highlight recent optimizations for analyzing FFPE tissues.
• To provide an overview of data analysis pipelines for chromatin accessibility studies.

Main Methods:

• Review of established high-throughput sequencing techniques (DNase-seq, MNase-seq, FAIRE-seq, ATAC-seq, NicE-seq).
• Discussion of recent technical advancements addressing FFPE tissue limitations.
• Outline of a typical bioinformatics pipeline for data analysis.

Main Results:

• FFPE tissues present significant challenges for chromatin accessibility assays due to crosslinking and DNA damage.
• Optimized protocols are emerging to enable reliable chromatin mapping in FFPE samples.
• Standardized data analysis pipelines are essential for consistent interpretation.

Conclusions:

• Mapping chromatin accessibility in FFPE tissues is becoming feasible with optimized methods.
• Understanding these patterns in FFPE samples can unlock insights into disease mechanisms.
• Further development and standardization of FFPE-based chromatin accessibility studies are warranted.