Abstract
Methylation on histone H3 lysine 4 (H3K4) correlates with actively transcribed genes. In mammalian cells, there exist multiple Set1-like histone H3K4 methyltransferase complexes, which have overlapping but distinct subunit compositions. Developing methods to isolate each of these histone H3K4 methyltransferase complexes would help understand the molecular mechanisms by which histone H3K4 methylation regulates mammalian gene expression. In this chapter, we provide a one-step affinity purification protocol on isolation of the MLL3/MLL4 histone H3K4 methyltransferase complex using FLAG-tagged PA1, a unique subunit of the MLL3/MLL4 complex.