Plant homeodomain fingers form a helping hand for transcription.
Plant homeodomain fingers form a helping hand for transcription.
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DOI：
10.4161/epi.6.1.13297
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发表时间：
2011-01
期刊：
影响因子：
3.7
通讯作者：
Shiekhattar R
中科院分区：
文献类型：
--
作者：
Fortschegger K;Shiekhattar R
几个最近的出版物证明了植物同源结构域指的亚组的共激活子功能，其在人类中包括PHF 2、PHF 8和KIAA 1718。除了N-末端植物同源结构域（PHD）之外，这些蛋白还具有酶活性Jumonji-C结构域（JmjC）。虽然它们已显示通过其PHD结合到活性基因启动子处的携带H3 K4 me 3的核小体，但它们的JmjC结构域能够去除组蛋白H3上的单-和二甲基-赖氨酸9或27，或组蛋白H4上的单甲基-赖氨酸20，与转录抑制相关的染色质修饰。这样的双重组蛋白串扰确保了在RNA聚合酶I和II的转录激活后抑制性组蛋白标记的适当去除。PHF 8基因的突变导致X连锁精神发育迟滞（XLMR），并且在斑马鱼中敲低KIAA 1718和PHF 8同源物导致脑缺陷。因此，这类新的染色质修饰酶的共激活剂功能在神经元发育中具有重要的功能作用。为了继续组蛋白去甲基化酶的命名法，我们建议KIAA 1718、PHF 8和PHF 2蛋白分别使用KDM 7A、-B和-C。
Several recent publications demonstrate a co-activator function for a subgroup of plant homeodomain fingers, which in humans comprises PHF2, PHF8 and KIAA1718. Besides an N-terminal plant homeodomain (PHD) these proteins also harbor an enzymatically active Jumonji-C domain (JmjC). While they have been shown to bind via their PHDs to H3K4me3-bearing nucleosomes at active gene promoters, their JmjC-domains are able to remove mono- and dimethyl-lysine 9 or 27 on histone H3, or monomethyl-lysine 20 on histone H4, chromatin modifications which correlate with transcriptional repression. Such dual histone crosstalk insures the proper removal of repressive histone marks following transcriptional activation by RNA polymerases I and II. Mutations in the PHF8 gene lead to X-linked mental retardation (XLMR) and knockdown of KIAA1718 and PHF8 homologs in zebrafish causes brain defects. Thus, the co-activator function of this new class of chromatin modifying enzymes has important functional roles in neuronal development. To continue with the nomenclature for histone demethylases, we propose the usage of KDM7A, -B and -C for KIAA1718, PHF8 and PHF2 proteins, respectively.