Laser Capture Microdissection Followed by Histone H1 Variant Analysis by Mass Spectrometry

The histone H1 family comprises of essential components of chromatin, which bind to the linker DNA connecting individual nucleosomes and contribute to the formation of higher-order chromatin structures. Multiple histone H1 exist, each with distinct interactions with the nucleosome that specifically influence chromatin organization and nuclear functions. Histone H1 variants have been shown to play a role as drivers in cancer and may serve as biomarkers for patient stratification. To overcome the limitations associated with antibody- and RNA-based methods for analyzing histone H1, we developed a mass spectrometry (MS)-based label-free approach to simultaneously analyze all somatic histone H1 variants in patient-derived samples. Here, we describe how this method can be used for the analysis of low-amount clinical samples obtained through laser capture microdissection of tissue sections.