Identification of a new family of higher eukaryotic histone deacetylases -Coordinate expression of differentiation-dependent chromatin modifiers

The histone deacetylase domain of almost all members of higher eukaryotic h istone deacetylases already identified (HDAC family) is highly homologous t o that of yeast RPD3.In this paper we report the cloning of two cDNAs encod ing members of a new family of histone deacetylase in mouse that show a bet ter homology to yeast HDA1 histone deacetylase, These cDNAs encode relative ly large proteins, presenting an in vitro trichostatin A-sensitive histone deacetylase activity. Interestingly, one, mHDA2, encodes a protein with two putative deacetylase domains, and the other, mHDA1, contains only one deac etylase homology domain, located at the C-terminal half of the protein, Our data showed that these newly identified genes could belong to a network. o f genes coordinately regulated and involved in the remodeling of chromatin during cell differentiation. Indeed, the expression of mHDA1 and mHDA2 is t ightly linked to the state of cell differentiation, behaving therefore like the histone H1 degrees-encoding gene. Moreover, like histone H1 degrees ge ne, mHDA1 and mHDA2 gene expression is induced upon deacetylase inhibitor t reatment, We postulate the existence of a regulatory mechanism, commanding a coordinate expression of a group of genes involved in the remodeling of c hromatin not only during cell differentiation but also after abnormal histo ne acetylation.