Analysis of CREM-dependent gene expression during mouse spermatogenesis

Analysis of CREM-dependent gene expression during mouse spermatogenesis
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DOI:
10.1016/j.mce.2003.09.023
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发表时间:
2003-12-30
影响因子:
4.1
通讯作者:
Schütz, G
Schütz, G
中科院分区:
医学2区
文献类型:
--
作者:
Beissbarth, T;Borisevich, I;Schütz, G

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转录因子CREM、CREB和ATF-1构成p-Zip转录因子的亚家族。几种不同的激酶级联调节这些蛋白质的活性。激活剂剪接异构体CREMtau在小鼠精子发生过程中在减数分裂后的生殖细胞中特异性且高度表达。缺乏CREMtau表达的雄性小鼠是不育的,因为精子细胞经历凋亡时精子成熟的阶段特异性停滞。为了表征圆形精子细胞减数分裂后分化期间由CREM控制的基因,我们通过抑制性消减杂交(SSH)比较了从野生型和CREM缺陷小鼠睾丸中制备的mRNA的表达水平。在CREM SSH文库中发现的一组956个独特序列通过使用尼龙DNA阵列与来自青春期前小鼠在精子发生的确定阶段的cDNA杂交产生精子发生期间的阶段特异性表达谱来进一步表征。我们的数据表明,当CREM活性最大时,大量基因在圆形精子细胞中被转录激活,包括转录因子、参与信号转导的蛋白质和代谢酶等功能基团,因此提供了许多已知的以及直接或间接受CREM表达影响的新基因的减数分裂后表达的新信息。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
The transcription factors CREM, CREB, and ATF-1 constitute a subfamily of p-Zip, transcription factors. Several different kinase cascades regulate the activity of these proteins. The activator splice-isoform CREMtau is specifically and highly expressed in post-meiotic germ cells during mouse spermatogenesis. Male mice lacking CREMtau expression are sterile because of stage-specific arrest of sperm maturation as the spermatids undergo apoptosis.In order to characterize the genes that are controlled by CREM during post-meiotic differentiation of round spermatids, we compared the expression levels of mRNA prepared from testes of wild-type and CREM-deficient mice by suppression subtractive hybridization (SSH) and affymetrix oligonucleotide arrays.A set of 956 unique sequences found in the CREM SSH library was further characterized by generating stage-specific expression profiles during spermatogenesis by hybridization with cDNA from pre-pubertal mice at defined stages of spermatogenesis using nylon DNA arrays. The resulting expression profiles were arranged in a linear order according to similarity in their profile shapes to find co-regulation of functionally related genes.Our data shows that a large number of genes are transcriptionally activated in round spermatids when CREM activity is maximal, including functional groups like transcription factors, proteins involved in signal transduction, and metabolic enzymes, therefore providing novel information of post-meiotic expression of many known as well as novel genes that are either directly or indirectly influenced by CREM expression. (C) 2003 Elsevier Ireland Ltd. All rights reserved.