Chromatin Immunoprecipitation Sequencing and RNA Sequencing from Laser-Microdissected Human Lung Cancer Cells

Genomic and epigenomic analyses are widely used in various biomedical research fields, with chromatin immunoprecipitation sequencing (ChIP-seq) representing one of the key techniques. The regulatory state of chromatin is crucial for understanding gene regulation mechanisms and the roles of transcription factors, and observing these states within native tissues using clinical specimens is particularly meaningful. One of the major advantages of ChIP-seq is its ability to comprehensively map histone modifications and transcription factor binding across the genome, especially those associated with specific functions. Additionally, it enables direct sequencing of genomic regions surrounding these modifications. Unlike techniques such as Assays for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), which involve enzymatic digestion of nearby DNA, ChIP-seq preserves the surrounding DNA, allowing for the identification of nucleotide sequences adjacent to target proteins or histone modifications. This feature makes it especially effective for detecting single nucleotide polymorphisms (SNPs) and somatic mutations associated with allele-specific transcription factor binding or histone marks. This chapter describes a method for ChIP-seq analysis of clinical lung cancer tissue samples isolated by laser microdissection. The method is also compatible with RNA isolation and subsequent RNA-seq, enabling the acquisition of cancer cell-specific epigenomic profiles within heterogeneous tissue environments.