CARM1

CARM1, also known as PRMT4 (protein arginine methyltransferase 4) or coactivator-associated arginine methyltransferase 1, is a nuclear enzyme that methylates arginine residues on histone and non-histone proteins. It belongs to the type I family of protein arginine methyltransferases and catalyzes asymmetric dimethylation of arginine residues.

Histone substrates are among its best characterized targets. CARM1 generates marks such as H3R17me2a and H3R26me2a, which are associated with active transcription. It also methylates non-histone proteins, including transcriptional coactivators and components of chromatin remodeling complexes such as SWI/SNF, influencing the activity of transcriptional programs.

As a transcriptional coactivator, CARM1 enhances gene expression by modifying chromatin and facilitating recruitment of the transcriptional machinery. It often cooperates with nuclear receptors, including estrogen and progesterone receptors, and with coactivators like CBP/p300. Through histone and non-histone methylation, CARM1 can affect chromatin structure and accessibility, thereby modulating transcriptional outcomes.

Biological roles for CARM1 include involvement in vertebrate development, where it is important for embryogenesis and lineage specification. Genetic disruption of CARM1 in model organisms produces developmental defects, underscoring its contribution to normal gene expression programs.

Clinical and research contexts describe dysregulation of CARM1 expression or activity in several cancers and metabolic diseases, with effects that appear context-dependent. Consequently, CARM1 is a focus of therapeutic interest, and small-molecule inhibitors and other strategies have been explored in preclinical studies as potential cancer treatments.