Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases

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Abstract

It has been widely debated whether class IIa HDACs have catalytic deacetylase activity, and whether this plays any part in controlling gene expression. Herein, it has been demonstrated that class IIa HDACs isolated from mammalian cells are contaminated with other deacetylases, but can be prepared cleanly in Escherichia coli. These bacteria preparations have weak but measurable deacetylase activity. The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors.

Graphical abstract

Bacteria preparations of HDAC4 have weak but measurable deacetylase activity, the low efficiency can be restored either by mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate.

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