MIR sequences recruit zinc finger protein ZNF768 to expressed genes
MIR sequences recruit zinc finger protein ZNF768 to expressed genes
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DOI：
10.1093/nar/gky1148
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发表时间：
2019-01-25
影响因子：
14.9
通讯作者：
Eick, Dirk
中科院分区：
文献类型：
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作者：
Rohrmoser, Michaela;Kluge, Michael;Eick, Dirk
哺乳动物广泛的散布重复序列（MIRs）是哺乳动物基因组的反转录转座元件。在这里，我们报告了锌指蛋白ZNF 768与MIRs核心区序列基序GCTGTGTG（N-20）CCTCTG的特异性结合。ZNF 768的结合优先与常染色质和基因启动子区相关。在人B细胞系Raji和骨肉瘤U2 OS细胞中观察到以细胞类型特异性方式表达的基因的结合。质谱分析显示ZNF 768与Elongator组分Elp 1、Elp 2和Elp 3以及其他核因子结合。ZNF 768的N-末端含有一个与RNA聚合酶II的C-末端结构域（CTD）结构相关的七肽重复序列。这个阵列在胎盘动物中进化，但不是有袋动物和单孔类动物，显示物种特异性的长度变化，并可能履行CTD相关的基因调控功能。我们认为MIRs和ZNF 768的进化扩展了哺乳动物的基因调控机制，ZNF 768的结合与细胞类型特异性基因表达有关。
Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N-20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.