title: dLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro-apoptotic gene hid.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Bhaskar
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Satya
authors.initials: S
authors.lastname: Surabhi
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Bipin Kumar
authors.initials: BK
authors.lastname: Tripathi
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Ashim
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India. Electronic address: mousumi_mutsuddi@yahoo.com.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Mutsuddi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology*; D050684:E2F Transcription Factors / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; C108880:HID protein, Drosophila; D009479:Neuropeptides; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C410902:lin protein, Drosophila
keywords: Apoptosis; dE2F1; dE2F2; dLin52; dRBF; hid