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Analysis of CREM-dependent gene expression during mouse spermatogenesis.
Tim Beissbarth1, Igor Borisevich, Andreas Hörlein
1Molecular Biology of the Cell 1, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. tim.beissbarth@molgen.mpg.de
Molecular and Cellular Endocrinology
|December 5, 2003
Summary
The cAMP response element modulator (CREM) transcription factor is crucial for male fertility. Its absence causes sterility due to germ cell apoptosis, highlighting CREM's role in sperm maturation.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Gene Regulation
Background:
- CREM, CREB, and ATF-1 are beta-Zip transcription factors regulating gene expression.
- CREMtau, an activator splice-isoform, is vital for mouse spermatogenesis.
- CREMtau deficiency leads to male sterility via spermatid apoptosis.
Purpose of the Study:
- To identify genes regulated by CREM during post-meiotic germ cell differentiation.
- To understand the molecular mechanisms underlying CREM-mediated spermatogenesis.
Main Methods:
- Suppression subtractive hybridization (SSH) to compare gene expression in wild-type and CREM-deficient mouse testes.
- Affymetrix oligonucleotide arrays and nylon DNA arrays for detailed expression profiling.
- Analysis of stage-specific expression patterns to identify co-regulated gene networks.
Main Results:
- Identified 956 unique sequences regulated by CREM.
- Revealed significant transcriptional activation of numerous genes in round spermatids when CREM activity is maximal.
- Discovered CREM influences functional groups including transcription factors, signal transduction proteins, and metabolic enzymes.
Conclusions:
- CREM plays a critical role in the transcriptional control of post-meiotic gene expression during spermatogenesis.
- Provides novel insights into genes directly and indirectly influenced by CREM.
- Establishes CREM as a key regulator of male germ cell differentiation and fertility.