Verdel A, Khochbin S
Laboratoire de Biologie Moléculaire du Cycle Cellulaire, INSERM U309, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France.
J Biol Chem. 1999 Jan 22;274(4):2440-5. doi: 10.1074/jbc.274.4.2440.
The histone deacetylase domain of almost all members of higher eukaryotic histone deacetylases already identified (HDAC family) is highly homologous to that of yeast RPD3. In this paper we report the cloning of two cDNAs encoding members of a new family of histone deacetylase in mouse that show a better homology to yeast HDA1 histone deacetylase. These cDNAs encode relatively 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 deacetylase homology domain, located at the C-terminal half of the protein. Our data showed that these newly identified genes could belong to a network of genes coordinately regulated and involved in the remodeling of chromatin during cell differentiation. Indeed, the expression of mHDA1 and mHDA2 is tightly linked to the state of cell differentiation, behaving therefore like the histone H1 degrees-encoding gene. Moreover, like histone H1(0) gene, mHDA1 and mHDA2 gene expression is induced upon deacetylase inhibitor treatment. We postulate the existence of a regulatory mechanism, commanding a coordinate expression of a group of genes involved in the remodeling of chromatin not only during cell differentiation but also after abnormal histone acetylation.
几乎所有已鉴定的高等真核生物组蛋白去乙酰化酶（HDAC家族）成员的组蛋白去乙酰化酶结构域都与酵母RPD3的该结构域高度同源。在本文中，我们报道了在小鼠中克隆出两个编码新型组蛋白去乙酰化酶家族成员的cDNA，它们与酵母HDA1组蛋白去乙酰化酶具有更好的同源性。这些cDNA编码相对较大的蛋白质，具有体外曲古抑菌素A敏感的组蛋白去乙酰化酶活性。有趣的是，其中一个，即mHDA2，编码一种具有两个推定去乙酰化酶结构域的蛋白质，另一个，即mHDA1，仅包含一个去乙酰化酶同源结构域，位于该蛋白质的C末端一半处。我们的数据表明，这些新鉴定的基因可能属于一个基因网络，该网络在细胞分化过程中受到协调调控并参与染色质重塑。实际上，mHDA1和mHDA2的表达与细胞分化状态紧密相关，因此其表现类似于编码组蛋白H1°的基因。此外，与组蛋白H1(0)基因一样，mHDA1和mHDA2基因的表达在去乙酰化酶抑制剂处理后被诱导。我们推测存在一种调节机制，该机制不仅在细胞分化过程中，而且在异常组蛋白乙酰化后，指挥一组参与染色质重塑的基因的协调表达。
