TAILIEUCHUNG - Báo cáo khoa học: The C-terminal region of CHD3/ZFH interacts with the CIDD region of the Ets transcription factor ERM and represses transcription of the human presenilin 1 gene

Presenilins are required for the function of c-secretase: a multiprotein complex implicated in the development of Alzheimer’s disease (AD). We analyzed expression of the presenilin 1 (PS1) gene. We show that ERM recognizes avian erythroblastosis virus E26 oncogene homolog (Ets) motifs on the PS1 promoter located at)10, +90, +129 and +165, and activates PS1 transcription with promoter fragments containing or not the)10 Ets site. | ễFEBS Journal The C-terminal region of CHD3 ZFH interacts with the CIDD region of the Ets transcription factor ERM and represses transcription of the human presenilin 1 gene Martine Pastorcic1 and Hriday K. Das1 2 1 Department of Pharmacology Neuroscience University of North Texas Health Science Center at Fort Worth TX USA 2 Department of Molecular Biology Immunology and Institute of Cancer Research University of North Texas Health Science Center at Fort Worth TX USA Keywords CHD3 ERM presenilin-1 transcription yeast-two-hybrid Correspondence . Das Department of Pharmacology Neuroscience and Institute of Cancer Research University of North Texas Health Science Center at Fort Worth 3500 Camp Bowie Boulevard Fort Worth TX 76107 USA Fax 1 817 735 2091 Tel 1 817 735 5448 E-mail hdas@ Received 8 August 2006 revised 2 January 2007 accepted 9 January 2007 doi Presenilins are required for the function of y-secretase a multiprotein complex implicated in the development of Alzheimer s disease AD . We analyzed expression of the presenilin 1 PS1 gene. We show that ERM recognizes avian erythroblastosis virus E26 oncogene homolog Ets motifs on the PS1 promoter located at -10 90 129 and 165 and activates PS1 transcription with promoter fragments containing or not the -10 Ets site. Using yeast two-hybrid selection we identified interactions between the chromatin remodeling factor CHD3 ZFH and the C-terminal 415 amino acids of ERM used as bait. Clones contained the C-terminal region of CHD3 starting from amino acid 1676. This C-terminal fragment amino acids 1676-2000 repressed transcription of the PS1 gene in transfection assays and PS1 protein expression from the endogenous gene in SH-SY5Y cells. In cells transfected with both CHD3 and ERM activation of PS1 transcription by ERM was eliminated with increasing levels of CHD3. Progressive N-terminal deletions of CHD3 fragment amino acids 1676-2000 indicated that sequences crucial for .

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