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首页> 外文期刊>Molecular and Cellular Biology >Eos, MITF, and PU.1 Recruit Corepressors to Osteoclast-Specific Genes in Committed Myeloid Progenitors
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Eos, MITF, and PU.1 Recruit Corepressors to Osteoclast-Specific Genes in Committed Myeloid Progenitors

机译：Eos，MITF和PU.1招募致力于骨髓祖细胞中破骨细胞特异基因的镇静剂

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摘要

Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.
机译：转录因子MITF和PU.1协同合作以增加靶基因的表达，如 cathepsin K （ Ctsk ）和酸性磷酸酶5 （ Acp5 ）。我们表明，这些因素还可以抑制能够形成巨噬细胞或破骨细胞的定型骨髓前体中靶基因的转录。 MITF和PU.1与Ikaros家族成员锌指蛋白Eos的直接相互作用对于抑制 Ctsk 和 Acp5 是必需的。 Eos在目标基因启动子上与MITF和PU.1形成复合物，并通过募集共表达CtBP（C末端结合蛋白）和Sin3A抑制转录，但在破骨细胞分化过程中，Eos与 Ctsk 和< em> Acp5 启动子明显减少。随后，MITF和PU.1向这些靶基因募集了共激活因子，从而使靶基因得以稳定表达。 Eos在骨髓来源的前体中的过度表达破坏破骨细胞分化并选择性抑制MITF / PU.1目标的转录，而Eos的RNA干扰较小则导致 Ctsk 和 Acp5的基础表达增加。这项工作提供了一种机制，用于在破骨细胞分化开始之前，响应于适当的细胞外信号，在定型的骨髓祖细胞中调节了MITF和PU.1的活性。

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