Cancer Science Institute of Singapore, National University of Singapore, Singapore
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Haematologica. 2018 Aug;103(8):1269-1277. doi: 10.3324/haematol.2018.190280. Epub 2018 May 17.
Maturation of granulocytes is dependent on controlled gene expression by myeloid lineage restricted transcription factors. CEBPE is one of the essential transcription factors required for granulocytic differentiation. Identification of downstream targets of CEBPE is vital to understand better its role in terminal granulopoiesis. In this study, we have identified as a novel target of CEBPE. We show that CEBPE binds to regulatory elements upstream of the murine locus, and expression of CARD10 is significantly reduced in knock-out mice. Silencing in a human cell line and in murine primary cells impaired granulopoiesis, affecting expression of genes involved in myeloid cell development and function. Taken together, our data demonstrate for the first time that is expressed in granulocytes and is a direct target of CEBPE with functions extending to myeloid differentiation.
粒细胞的成熟依赖于髓系谱系限制转录因子的受控基因表达。CEBPE 是粒细胞分化所必需的关键转录因子之一。鉴定 CEBPE 的下游靶标对于更好地理解其在终末粒细胞生成中的作用至关重要。在这项研究中,我们鉴定了 为 CEBPE 的一个新靶标。我们表明,CEBPE 与鼠 基因座上游的调节元件结合,并且在 敲除小鼠中 的表达显著降低。在人细胞系和鼠原代细胞中沉默 会损害粒细胞生成,影响参与髓样细胞发育和功能的基因的表达。总之,我们的数据首次表明, 在粒细胞中表达,是 CEBPE 的直接靶标,其功能扩展到髓样分化。