PU.1转录因子调控前体脂肪细胞生脂的分子机制研究进展

PU.1转录因子是保守的DNA结合蛋白Ets家族成员,因其DNA结合区识别共有序列GAGGAA,故该区又称为Ets结合区或PU.1box。PU.1主要在造血系统如髓细胞和B淋巴细胞中表达,调节关键髓系基因的转录从而调控造血系统的分化。PU.1周身敲除后,由于胎儿肝脏中缺乏B淋巴细胞和髓系细胞,导致小鼠胚胎早期死亡,表明PU.1是调控生命过程的关键转录因子。目前,在脂肪细胞中PU.1对脂肪生成作用及机制的研究报道较少。PU.1与脂肪细胞脂肪生成,与miRNAs、antisense RNA以及C/EBPα/β-PPARγ通路的调控关系将是今后研究的重点。     

Spi-B can functionally replace PU.1 in myeloid but not lymphoid development

Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1(-/-) mice. In contrast, mice lacking the highly related protein Spi-B generate all hematopoietic lineages but display a B-cell receptor signaling defect. These distinct phenotypes could result from functional differences between PU.1 and Spi-B or their unique temporal and tissue-specific expression (PU.1: myeloid and B cells; Spi-B: B cells only). To address this question, we introduced the Spi-B cDNA into the murine PU.1 locus by homologous recombination. In the absence of PU.1, Spi-B rescued macrophage and granulocyte development when assayed by in vitro differentiation of embryonic stem cells. Adherent, CD11b(+)/F4/80(+) cells capable of phagocytosis were detected in PU.1(Spi-B/Spi-B) embryoid bodies, and myeloid colonies were present in hematopoietic progenitor assays. Despite its ability to rescue myeloid differentiation, Spi-B did not rescue lymphoid development in a RAG-2(-/-) complementation assay. These results demonstrate an important difference between PU.1 and Spi-B. Careful comparison of these Ets factors will delineate important functional domains of PU.1 involved in lymphocyte lineage commitment and/or maturation.