Recently developed biochemical techniques have enabled researchers to study 
histone modifications more easily and accurately. One of these modifications, 
histone lysine methylation, has been shown to be highly stable and to represent 
an epigenetic alteration. Extensive biochemical analyses have led to discoveries 
about the nature and functions of this modification, thus accelerating our 
understanding of this crucial epigenetic event. Here we describe basic methods 
for purification and biochemical analysis of lysine-directed, histone 
methyltransferases from HeLa cell-derived extracts. In the section on substrate 
preparation, we describe a simple method for the preparation of recombinant 
substrates, although we recommend using native substrates for initial detection 
of the activities. The purification protocols for several histone 
methyltransferases have been streamlined so that those researchers with a basic 
understanding of biochemistry can perform them. We also describe many tips and 
provide suggestions to avoid common pitfalls in the biochemical analysis of 
histone methyltransferases.