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Nagamori I , Yomogida K , Adams PD , Sassone-Corsi P , Nojima H
Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act in concert in postmeiotic transcriptional regulation
JOURNAL OF BIOLOGICAL CHEMISTRY. 2006 Jun;281(22) :15073-15081
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We previously isolated 80 TISP ( transcript induced in spermiogenesis) genes whose transcription is dramatically induced during spermiogenesis. Our analysis here of the expression of these genes in the testis of the cAMP-responsive element modulator(CREM)-nullmouse revealed that 54 TISP genes are under the transcriptional regulation of CREM. One CREM-regulated gene is TISP40, which encodes a basic leucine zipper (bZip)-type transcription factor bearing a transmembrane domain that generates the two proteins Tisp40 alpha and Tisp40 beta. Both of these proteins function by binding to UPRE( unfolded protein-response element) but do not recognize CRE motifs. We show here that Tisp40 alpha mRNA is generated under the direct transcriptional regulation of CREM. CREM tau and Tisp40 form a heterodimer, which functions through CRE but not through UPRE. Furthermore, binding ability of CREM to CRE is dramatically up-regulated by forming a heterodimer with Tisp40 alpha Delta TM, a truncat! ed form of Tisp40 alpha that lacks the transmembrane domain. We confirmed that Tisp40 and CREM actually bind to the Tisp40 promoter in vivo by chromatin immunoprecipitation assay. Finally, we demonstrate that the Tisp40 Delta TM-CREM tau heterodimer acts as a recruiter of HIRA, a histone chaperone, to CRE. Taken together, we propose that Tisp40 is an important transcriptional regulator during spermiogenesis.