A MAMMALIAN HISTONE DEACETYLASE RELATED TO THE YEAST TRANSCRIPTIONAL REGULATOR RPD3P

Trapoxin is a microbially derived cyclotetrapeptide that inhibits hist one deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both prot eins were identified by peptide microsequencing, and a complementary D NA encoding the histone deacetylase catalytic subunit (HD1) was cloned from a human Jurkat T cell library. As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results su pport a role for histone deacetylase as a key regulator of eukaryotic transcription.