DISTINCT DNA-BINDING PROPERTIES OF THE HIGH-MOBILITY GROUP DOMAIN OF MURINE AND HUMAN SRY SEX-DETERMINING FACTORS
DISTINCT DNA-BINDING PROPERTIES OF THE HIGH-MOBILITY GROUP DOMAIN OF MURINE AND HUMAN SRY SEX-DETERMINING FACTORS
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DOI：
10.1073/pnas.91.8.3368
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
GROSSCHEDL, R
中科院分区：
文献类型：
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作者：
GIESE, K;PAGEL, J;GROSSCHEDL, R
哺乳动物性别决定基因SRY（Y染色体上的性别决定区）编码调节蛋白的高迁移率族（HMG）家族的一个成员。SRY蛋白的HMG结构域代表一种DNA结合基序，在人类和小鼠的序列之间，其氨基酸表现出相当不寻常的弱进化保守性。再加上先前发现人类（h）SRY基因无法在基因雌性转基因小鼠中诱导出雄性表型，这些观察结果引发了有关SRY蛋白DNA结合特性的问题。在此，我们提供的数据表明，小鼠（m）SRY和hSRY的HMG结构域的DNA结合和弯曲特性彼此不同。相比之下，mSRY与DNA的大沟接触更广泛，并且比hSRY具有更高的序列识别特异性。此外，hSRY和mSRY的HMG结构域对蛋白质诱导的DNA弯曲程度不同。hSRY和mSRY在DNA结合方面的这些差异可能在一定程度上解释了这些基因产物所观察到的功能差异。
The mammalian sex-determining gene SRY (sex-determining region on Y chromosome) encodes a member of the high mobility group (HMG) family of regulatory proteins. The HMG domain of the SRY protein represents a DNA binding motif that displays rather unusually weak evolutionary conservation of amino acids between human and mouse sequences. Together with the previous finding that the human (h) SRY gene is unable to induce a male phenotype in genetically female transgenic mice, these observations raise questions concerning the DNA binding properties of SRY proteins. Here, we present data that indicate that the DNA binding and bending properties of the HMG domains of murine (m) SRY and hSRY differ from each other. In comparison, mSRY shows more-extensive major-groove contacts with DNA and a higher specificity of sequence recognition than hSRY. Moreover, the extent of protein-induced DNA bending differs for the HMG domains of hSRY and mSRY. These differences in DNA binding by hSRY and mSRY may, in part, account for the functional differences observed with these gene products.