Viiri Keijo M, Jänis Janne, Siggers Trevor, Heinonen Taisto Y K, Valjakka Jarkko, Bulyk Martha L, Mäki Markku, Lohi Olli
Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital, 33520 Tampere, Finland.
Mol Cell Biol. 2009 Jan;29(2):342-56. doi: 10.1128/MCB.01213-08. Epub 2008 Nov 17.
Deacetylation of histones is carried out by a corepressor complex in which Sin3A is an essential scaffold protein. Two proteins in this complex, the Sin3A-associated proteins SAP30L and SAP30, have previously been suggested to function as linker molecules between various corepressors. In this report, we demonstrate new functions for human SAP30L and SAP30 by showing that they can associate directly with core histones as well as naked DNA. A zinc-coordinating structure is necessary for DNA binding, one consequence of which is bending of the DNA. We provide evidence that a sequence motif previously shown to be a nuclear localization signal is also a phosphatidylinositol (PI)-binding element and that binding of specific nuclear monophosphoinositides regulates DNA binding and chromatin association of SAP30L. PI binding also decreases the repression activity of SAP30L and affects its translocation from the nucleus to the cytoplasm. Our results suggest that SAP30L and SAP30 play active roles in recruitment of deacetylating enzymes to nucleosomes, and mediate key protein-protein and protein-DNA interactions involved in chromatin remodeling and transcription.
组蛋白的去乙酰化由一个共抑制复合物完成，其中Sin3A是一种必需的支架蛋白。该复合物中的两种蛋白，即Sin3A相关蛋白SAP30L和SAP30，此前被认为作为各种共抑制因子之间的连接分子发挥作用。在本报告中，我们通过证明人SAP30L和SAP30能直接与核心组蛋白以及裸露的DNA结合，揭示了它们的新功能。锌配位结构对于DNA结合是必需的，其结果之一是DNA弯曲。我们提供的证据表明，一个先前被证明是核定位信号的序列基序也是磷脂酰肌醇（PI）结合元件，并且特定核单磷酸肌醇的结合调节SAP30L的DNA结合和染色质结合。PI结合还降低了SAP30L的抑制活性，并影响其从细胞核到细胞质的转运。我们的结果表明，SAP30L和SAP30在将去乙酰化酶募集到核小体中发挥积极作用，并介导参与染色质重塑和转录的关键蛋白-蛋白和蛋白-DNA相互作用。
