早幼粒細胞白血病鋅指蛋白(Promyelocytic Leukemia Zinc Finger; PLZF)是一Kruppel-like鋅指蛋白基因，先前在具多種染色體易位 t(11:17)(q23;q21)以及少數對all-trans-retinoic acid (ATRA)治療沒有反應的罕見急性前骨髓性白血球症病人中被識別出來。PLZF是一轉錄抑制因子，會結合到許多基因的啟動子上，例如cyclin A2和c-myc，影響其基因的表現。PLZF在發育中的肢芽(limb bud)、睪丸、中樞神經系統以及血球前趨細胞中皆有高度表現，並隨著細胞分化而逐漸降低其表現。PLZF的生理功能主要與幹細胞的維持有關，包括血球幹細胞和精原幹細胞，同時對血球新生和精細胞的發育過程扮演重要功能，且和四肢及軀幹的骨骼形成相關。然而，目前對於PLZF是否影響腦部的發育過程並不清楚，先前的研究結果顯示PLZF同樣在胚胎腦部發育過程中有高度的表現，並隨著發育過程受到嚴格的調控，顯示PLZF對腦部發育可能也扮演了重要的角色。雖然PLZF的功能如此重要，但其基因表現相關的調控機制到目前為止仍未清楚的被研究。我們以P19細胞作為神經分化模型，發現PLZF在P19細胞神經分化早期有高度的表現，而在P19細胞神經分化晚期逐漸消失。在進一步的研究中，我們發現小鼠的Plzf基因具有一種以上的transcripts，同時我們也找到了Plzf基因的其中一個啟動子。此外，我們發現已知對於胚胎發育以及神經前驅細胞自我更新能力皆相當重要的基因─E2F1，可以活化Plzf基因的啟動子活性，實驗結果顯示在胚胎神經系統發育過程中，Plzf基因的表現可能受到E2F1的調控。

The promyelocytic leukemia zinc finger (PLZF) is a Kruppel-like zinc finger gene previously identified in a rare case of acute promyelocytic leukemia (APL) with a variant chromosomal translocation t(11:17)(q23;q21) and resistance to therapy with all-trans-retinoic acid (ATRA). PLZF is a transcriptional repressor that binds to the promoter of various genes, such as cyclin A2 and c-myc. PLZF is highly expressed in developing limb, testis, central nervous system, and hematopoietic progenitor cells, and is downregulated during cell differentiation. The physiological function of PLZF is to maintain the stem cells of various lineages, such as hematopoietic stem cells and spermatogonial stem cells, and is implicated in development of hematopoiesis and germ cells, and regulating limb and axial skeletal patterning. The functional role of PLZF in brain development is less studied, but previous reports showed that PLZF expresses in spatially restricted and temporally dynamic patterns in the central nervous system. It suggests that PLZF may also play a role in the brain development. Although PLZF is important for embryo development, its regulation is poorly understood. Using P19 cells as the neuronal differentiation model, we found the expression of PLZF was induced at the early stage of neuronal differentiation in P19 cells and diminished at the late stage. In the further investigation, we identified more than one variant transcripts of the mouse Plzf gene in P19 cells and mouse tissues. We also identified one of the promoters of the mouse Plzf gene. Lastly, We found that E2F1, which was essential for the embryonic development and was indispensable for the self-renewal of neural progenitor cells, activated the promoter activity of mouse Plzf gene. Our results suggest that E2F1 may regulate Plzf gene expression during brain development.

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