H1f2, also known as H1c, is a gene encoding a linker histone H1 isoform. Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, which is crucial for maintaining the 3D chromatin architecture and regulating gene expression [1].

In mice, loss-of-function experiments by knocking out H1c (H1f2) and H1e (H1f4) showed that this disruption led to enhanced fitness and self-renewal properties in germinal centre B cells. The loss of H1 function caused profound architectural remodelling of the genome, with large-scale yet focal chromatin decompaction. This decompaction led to distinct epigenetic changes, such as a gain of H3K36me2 and/or loss of H3K27me3, unlocking the expression of stem cell genes normally silenced during early development, ultimately resulting in aggressive lymphomas with increased repopulating potential [1].

In conclusion, H1f2 is essential for sequestering early developmental genes into inaccessible genomic compartments through its role in chromatin compaction. The gene knockout mouse models have revealed that H1f2 loss drives malignant transformation in lymphomas, highlighting its role as a tumour suppressor. Understanding H1f2 function provides insights into lymphoma development and potential therapeutic targets.