H3K9me3 Controls Epidermis Morphogenesis by Regulating RNA Polymerase II Dynamics at Developmental Promoters and Enhancers

The study explores the role of H3K9me3 in epidermal morphogenesis, demonstrating its crucial function in regulating RNA Pol II dynamics at developmental promoters and enhancers. Using a mouse model with a triple knockout of histone methyltransferases responsible for H3K9me3 formation, the research found that the absence of H3K9me3 leads to significant defects in epidermal development, including impaired stratification, reduced epidermal thickness, and disrupted hair follicle and Merkel cell formation. H3K9me3 is essential for controlling cell adhesion, differentiation, proliferation, and metabolism during skin development by repressing non-lineage genes and orchestrating keratinocyte subtype-specific programs. The study highlights H3K9me3's role in maintaining epidermal lineage integrity and suggests its developmental role supports the complexity of mammalian organogenesis.