Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells
Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells
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DOI：
10.1074/jbc.m501423200
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Yamanaka, S
中科院分区：
文献类型：
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作者：
Maruyama, M;Ichisaka, T;Yamanaka, S
Sox家族转录因子在细胞分化、发育和性别决定中起重要作用。Sox 2以前被认为是小鼠胚胎干细胞（ES）中表达的唯一Sox蛋白。Sox 2与Oct 3/4结合以维持ES细胞的自我更新。在目前的研究中，数字差异显示确定了一个额外的Sox家族成员，Sox 15，在小鼠ES细胞富集的转录本。逆转录-PCR证实，Sox 15的表达是最高的未分化的ES细胞和抑制分化。Sox 15在几种组织中以低水平表达，包括睾丸和肌肉。体外研究表明，Sox 15与Sox 2一样，与含有八聚体基序和Sox结合位点的DNA序列上的Oct 3/4相关。凝胶迁移率变动分析和SELEX分析表明，Sox 15与Sox 2结合的DNA序列相似，但亲和力较弱。与在Sox 2缺失小鼠中观察到的早期胚胎致死率相反，Sox 15缺失ES细胞和小鼠大体正常。然而，DNA微阵列分析显示，Otx 2，Ctgf，Ebaf和Hrc在Sox 15缺失的ES细胞中失调。染色质免疫沉淀显示，Sox 15，但不是Sox 2，绑定到一个Sox的共识结合位点内的Hrc基因。综上所述，这些数据证明了Sox 15和Sox 2在小鼠ES细胞转录控制中的不同作用。
Sox family transcription factors play essential roles in cell differentiation, development, and sex determination. Sox2 was previously thought to be the sole Sox protein expressed in mouse embryonic stem (ES) cells. Sox2 associates with Oct3/4 to maintain self- renewal of ES cells. In the current study, digital differential display identified transcripts for an additional Sox family member, Sox15, enriched in mouse ES cells. Reverse transcription-PCR confirmed that Sox15 expression is highest in undifferentiated ES cells and repressed upon differentiation. Sox15 is expressed at low levels in several tissues, including testis and muscle. In vitro studies showed that Sox15, like Sox2, associated with Oct3/4 on DNA sequences containing the octamer motif and Sox-binding site. Gel mobility shift assays and SELEX analyses showed that Sox15 binds similar DNA sequences as Sox2 but with weaker affinity. In contrast to the early embryonic lethality observed in Sox2-null mice, Sox15-null ES cells and mice were grossly normal. DNA microarray analyses revealed that Otx2, Ctgf, Ebaf, and Hrc are dysregulated in Sox15-null ES cells, however. Chromatin immunoprecipitation showed that Sox15, but not Sox2, bound to a Sox consensus binding site within the Hrc gene. Taken together, these data demonstrate differential roles for Sox15 and Sox2 in transcriptional control in mouse ES cells.