Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1.
Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1.
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DOI：
10.1006/jmbi.2001.4569
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发表时间：
2001-04
影响因子：
5.6
通讯作者：
Jan Taplick;V. Kurtev;K. Kroboth;M. Posch;T. Lechner;C. Seiser
中科院分区：
文献类型：
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作者：
Jan Taplick;V. Kurtev;K. Kroboth;M. Posch;T. Lechner;C. Seiser
可逆的组蛋白乙酰化改变了染色质的结构，可以调节基因的转录。哺乳动物组蛋白去乙酰化酶1（HDAC 1）是一种核蛋白，其属于一个不断增长的进化上保守的酶家族，催化从核心组蛋白和其他蛋白质中去除乙酰基残基。以前，我们已经确定了小鼠HDAC 1作为一种生长因子诱导的蛋白在小鼠T细胞。在这里，我们更详细地阐述了小鼠HDAC 1的分子功能。用表位标记的HDAC 1蛋白的免疫共沉淀实验揭示了与内源性HDAC 1酶的关联。我们发现，HDAC 1可以同源寡聚化，这种相互作用是依赖于N-末端的HDAC协会结构域的蛋白质。此外，相同的HDAC 1结构域对于HDAC 2和HDAC 3的体外结合、与RbAp 48的结合以及酶的催化活性也是必需的。HDAC 1羧基端富含赖氨酸的序列对于酶的核定位至关重要。我们确定了一个C-末端核定位域，这是足够的HDAC 1和报告融合蛋白的运输到细胞核。或者，HDAC 1可以通过其N-末端HDAC缔合结构域与另一个HDAC 1分子缔合而穿梭进入细胞核。我们的研究结果定义了两个域，这是必不可少的寡聚化和小鼠HDAC 1的核定位。
Reversible histone acetylation changes the chromatin structure and can modulate gene transcription. Mammalian histone deacetylase 1 (HDAC1) is a nuclear protein that belongs to a growing family of evolutionarily conserved enzymes catalysing the removal of acetyl residues from core histones and other proteins. Previously, we have identified murine HDAC1 as a growth factor-inducible protein in murine T-cells. Here, we characterise the molecular function of mouse HDAC1 in more detail. Co-immunoprecipitation experiments with epitope-tagged HDAC1 protein reveal the association with endogenous HDAC1 enzyme. We show that HDAC1 can homo-oligomerise and that this interaction is dependent on the N-terminal HDAC association domain of the protein. Furthermore, the same HDAC1 domain is also necessary for in vitro binding of HDAC2 and HDAC3, association with RbAp48 and for catalytic activity of the enzyme. A lysine-rich sequence within the carboxy terminus of HDAC1 is crucial for nuclear localisation of the enzyme. We identify a C-terminal nuclear localisation domain, which is sufficient for the transport of HDAC1 and of reporter fusion proteins into the nucleus. Alternatively, HDAC1 can be shuttled into the nucleus by association with another HDAC1 molecule via its N-terminal HDAC association domain. Our results define two domains, which are essential for the oligomerisation and nuclear localisation of mouse HDAC1.