Bhaskar Pradeep Kumar, Surabhi Satya, Tripathi Bipin Kumar, Mukherjee Ashim, Mutsuddi Mousumi
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
Biochim Biophys Acta. 2014 Sep;1839(9):800-12. doi: 10.1016/j.bbagrm.2014.05.012. Epub 2014 May 24.
Drosophila lin52 (dlin52) is a member of Myb transcription regulator complex and it shows a dynamic pattern of expression in all Drosophila tissues. Myb complex functions to activate or repress transcription in a site-specific manner; however, the detailed mechanism is yet to be clearly understood. Members of the Drosophila melanogaster Myb-MuvB/dREAM complex have been known to regulate expression of a wide range of genes including those involved in regulating apoptosis. E2F and its corepressor RBF also belong to this complex and together they regulate expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. In the present study, we examined whether the depletion of dlin52 in developing photoreceptor neurons results in enhanced apoptosis and disorganisation of the ommatidia. Strikingly, we found that dLin52 is essential for transcriptional repression of the pro-apoptotic gene, hid; decrease in dlin52 levels led to dramatic induction of hid and apoptosis in eye-antennal discs. Reduction of Rpd3 (HDAC1), another member of the dREAM complex, also led to marginal upregulation of Hid. In addition, we also demonstrated that an optimum level of dLin52 is needed for dE2F1/2 activity on the hid promoter. dlin52 cooperates with dRBF and dE2F1/2 for recruitment of repressor complex on the hid promoter. Preliminary data indicate that Rpd3/HDAC1 also contributes to hid repression. Based on the findings, we conclude that dLin52 functions as a co-factor and modulates activity of members of dMyb/dREAM complex at hid promoter, thus regulating apoptosis by repressing this pro-apoptotic gene in the developing Drosophila eye.
果蝇lin52（dlin52）是Myb转录调节复合物的成员，在果蝇所有组织中呈现动态表达模式。Myb复合物以位点特异性方式激活或抑制转录；然而，其详细机制尚待明确。已知黑腹果蝇Myb-MuvB/dREAM复合物的成员可调节多种基因的表达，包括参与调节细胞凋亡的基因。E2F及其共抑制因子RBF也属于该复合物，它们共同调节参与细胞周期进程、细胞凋亡、分化和发育的基因的表达。在本研究中，我们检测了发育中的感光神经元中dlin52的缺失是否会导致细胞凋亡增加和小眼的紊乱。令人惊讶的是，我们发现dLin52对于促凋亡基因hid的转录抑制至关重要；dlin52水平的降低导致眼触角盘中hid的显著诱导和细胞凋亡。dREAM复合物的另一个成员Rpd3（HDAC1）的减少也导致Hid的轻微上调。此外，我们还证明了dLin52在hid启动子上的dE2F1/2活性需要最佳水平。dlin52与dRBF和dE2F1/2协同作用，在hid启动子上募集抑制复合物。初步数据表明Rpd3/HDAC1也有助于hid的抑制。基于这些发现，我们得出结论，dLin52作为一种辅助因子，在hid启动子上调节dMyb/dREAM复合物成员的活性，从而通过抑制果蝇发育中的眼睛中的这种促凋亡基因来调节细胞凋亡。
