Activating transcription factor 1 and CREB are important for cell survival during early mouse development
Activating transcription factor 1 and CREB are important for cell survival during early mouse development
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DOI：
10.1128/mcb.22.6.1919-1925.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Schütz, G
中科院分区：
文献类型：
--
作者：
Bleckmann, SC;Blendy, JA;Schütz, G
转录激活因子1（ATF 1）、CREB和环AMP（cAMP）反应元件调节蛋白（CREM）构成碱性亮氨酸拉链转录因子的亚家族，通过作为同源或异源二聚体与靶基因调控区的cAMP反应元件结合来激活基因表达。为了研究ATF 1在体内的功能，我们通过同源重组使相应的基因失活。相反，CREB缺陷的小鼠，遭受围产期死亡，缺乏ATF 1的小鼠不表现出任何明显的表型异常。由于ATF 1和CREB，而不是CREM强烈共表达在早期小鼠发育过程中，我们产生的小鼠CREB和ATF 1都缺乏。ATF 1（-/-）CREB-/-胚胎在着床前由于发育停滞而死亡。ATF 1（+/-）CREB-/-胚胎在胚胎第9.5天左右由于大量凋亡而显示胚胎致死的表型。这些结果表明，CREB和ATF 1协同作用，介导维持细胞活力在早期胚胎发育过程中必不可少的信号。
Activating transcription factor 1 (ATF1), CREB, and the cyclic AMP (cAMP) response element modulatory protein (CREM), which constitute a subfamily of the basic leucine zipper transcription factors, activate gene expression by binding as homo- or heterodimers to the cAMP response element in regulatory regions of target genes. To investigate the function of ATF1 in vivo, we inactivated the corresponding gene by homologous recombination. In contrast to CREB-deficient mice, which suffer from perinatal lethality, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities. Since ATF1 and CREB but not CREM are strongly coexpressed during early mouse development, we generated mice deficient for both CREB and ATF1. ATF1(-/-) CREB-/- embryos die before implantation due to developmental arrest. ATF1(+/-) CREB-/- embryos display a phenotype of embryonic lethality around embryonic day 9.5 due to massive apoptosis. These results indicate that CREB and ATF1 act in concert to mediate signals essential for maintaining cell viability during early embryonic development.