Fan Wei, Lam Sin Man, Xin Jingxue, Yang Xiao, Liu Zhonghua, Liu Yuan, Wang Yong, Shui Guanghou, Huang Xun
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
PLoS Genet. 2017 Mar 8;13(3):e1006664. doi: 10.1371/journal.pgen.1006664. eCollection 2017 Mar.
The general transcription factor TBP (TATA-box binding protein) and its associated factors (TAFs) together form the TFIID complex, which directs transcription initiation. Through RNAi and mutant analysis, we identified a specific TBP family protein, TRF2, and a set of TAFs that regulate lipid droplet (LD) size in the Drosophila larval fat body. Among the three Drosophila TBP genes, trf2, tbp and trf1, only loss of function of trf2 results in increased LD size. Moreover, TRF2 and TAF9 regulate fatty acid composition of several classes of phospholipids. Through RNA profiling, we found that TRF2 and TAF9 affects the transcription of a common set of genes, including peroxisomal fatty acid β-oxidation-related genes that affect phospholipid fatty acid composition. We also found that knockdown of several TRF2 and TAF9 target genes results in large LDs, a phenotype which is similar to that of trf2 mutants. Together, these findings provide new insights into the specific role of the general transcription machinery in lipid homeostasis.
通用转录因子TBP（TATA框结合蛋白）及其相关因子（TAFs）共同形成TFIID复合物，该复合物指导转录起始。通过RNA干扰和突变分析，我们鉴定出一种特定的TBP家族蛋白TRF2，以及一组在果蝇幼虫脂肪体中调节脂滴（LD）大小的TAFs。在果蝇的三个TBP基因trf2、tbp和trf1中，只有trf2功能丧失会导致LD大小增加。此外，TRF2和TAF9调节几类磷脂的脂肪酸组成。通过RNA分析，我们发现TRF2和TAF9影响一组共同基因的转录，包括影响磷脂脂肪酸组成的过氧化物酶体脂肪酸β-氧化相关基因。我们还发现，敲低几个TRF2和TAF9的靶基因会导致形成大的脂滴，这一表型与trf2突变体相似。总之，这些发现为通用转录机制在脂质稳态中的特定作用提供了新的见解。
