Rehli M, Lichanska A, Cassady A I, Ostrowski M C, Hume D A
Department of Microbiology, Centre for Molecular and Cellular Biology, University of Queensland, Brisbane, Australia.
J Immunol. 1999 Feb 1;162(3):1559-65.
The murine homologue of the TFEC was cloned as part of an analysis of the expression of the microphthalmia-TFE (MiT) subfamily of transcription factors in macrophages. TFEC, which most likely acts as a transcriptional repressor in heterodimers with other MiT family members, was identified in cells of the mononuclear phagocyte lineage, coexpressed with all other known MiT subfamily members (Mitf, TFE3, TFEB). Northern blot analysis of several different cell lineages indicated that the expression of murine TFEC (mTFEC) was restricted to macrophages. A 600-bp fragment of the TATA-less putative proximal promoter of TFEC shares features with many known macrophage-specific promoters and preferentially directs luciferase expression in the RAW264.7 macrophage cell line in transient transfection assays. Five of six putative Ets motifs identified in the TFEC promoter bind the macrophage-restricted transcription factor PU.1 under in vitro conditions and in transfected 3T3 fibroblasts; the minimal luciferase activity of the TFEC promoter could be induced by coexpression of PU.1 or the related transcription factor Ets-2. The functional importance of the tissue-restricted expression of TFEC and a possible role in macrophage-specific gene regulation require further investigation, but are likely to be linked to the role of the other MiT family members in this lineage.
作为对巨噬细胞中转录因子小眼畸形-TFE(MiT)亚家族表达分析的一部分,TFEC的小鼠同源物得以克隆。TFEC在单核吞噬细胞系的细胞中被鉴定出来,它最有可能在与其他MiT家族成员形成的异源二聚体中作为转录抑制因子发挥作用,并与所有其他已知的MiT亚家族成员(Mitf、TFE3、TFEB)共同表达。对几种不同细胞系的Northern印迹分析表明,小鼠TFEC(mTFEC)的表达仅限于巨噬细胞。TFEC无TATA框的假定近端启动子的一个600 bp片段与许多已知的巨噬细胞特异性启动子具有共同特征,并且在瞬时转染实验中优先指导荧光素酶在RAW264.7巨噬细胞系中的表达。在TFEC启动子中鉴定出的六个假定Ets基序中有五个在体外条件下以及在转染的3T3成纤维细胞中与巨噬细胞限制性转录因子PU.1结合;TFEC启动子的最小荧光素酶活性可通过共表达PU.1或相关转录因子Ets-2来诱导。TFEC组织限制性表达的功能重要性以及在巨噬细胞特异性基因调控中的可能作用需要进一步研究,但可能与该细胞系中其他MiT家族成员的作用有关。