TY - JOUR
T1 - DLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro-apoptotic gene hid
AU - Bhaskar, Pradeep Kumar
AU - Surabhi, Satya
AU - Tripathi, Bipin Kumar
AU - Mukherjee, Ashim
AU - Mutsuddi, Mousumi
N1 - Funding Information:
We would like to thank Drs. H. Steller, K. White, Wei Du, M. Botchan, Nick Dyson, and Terry Orr-Weaver, Vienna Drosophila RNAi Center, Bloomington Stock Center and Developmental Studies Hybridoma Bank at the University of Iowa for generously supplying reagents and stocks. National Confocal Facility, Department of Zoology and Instrumentation Facility at ISLS are duly acknowledged. We appreciate the suggestions provided by the anonymous reviewers and the editor which have helped us to improve the manuscript substantially. PKB was supported by UGC-Rajiv Gandhi National Fellowship, while SS and BKT were supported by SRF from CSIR, Government of India. We acknowledge funding provided by Department of Science and Technology, Government of India.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Apoptosis
KW - DE2F1
KW - DE2F2
KW - DLin52
KW - DRBF
KW - Hid
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U2 - 10.1016/j.bbagrm.2014.05.012
DO - 10.1016/j.bbagrm.2014.05.012
M3 - Article
C2 - 24863159
AN - SCOPUS:84904130224
SN - 1874-9399
VL - 1839
SP - 800
EP - 812
JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
IS - 9
ER -