Function of regulatory factors of transcription and DNA replication in relation to the F9 cell differentiation.

F9细胞经维甲酸处理后可诱导分化为内胚层样细胞。我们分析了几种转录和DNA复制调控因子在F9细胞分化中的作用.多瘤病毒突变体F9-5000的增强子缺失24个碱基，在F9细胞和经维甲酸诱导分化的细胞中均能发挥作用。DELTAF 9 -5000元件对应于增强子的缺失区域。该元件的功能是抑制F9细胞中的基因表达，并结合一种被认为负责抑制的因子PEBP 4。然而，在分化的细胞中，相同的元件增强基因表达并结合转录激活因子PEBP 2和PEBP 4。PEBP 2的识别序列与PEBP 4的识别序列部分重叠。PEBP 3（PEBP 2的去磷酸化形式）和PFBP 4实际上被证明竞争结合位点。一种普遍存在的负性因子与分化诱导的正性因子的相互作用可能代表了胚胎发育过程中基因调控的一个方面.转录激活因子AP 1是核原癌基因c-jun和c-fos产物的异源二聚体，在F9细胞中检测不到。发现激活的c-Ha-ras癌基因可诱导F9细胞的AP 1活性。这种诱导似乎是由于c-jun基因转录的诱导。激活的c-Ha-ras和c-jun基因均能诱导F9细胞向内胚层样细胞分化，AP 1在Fg细胞分化的初期起关键作用。

F9 cells can be induced to differentiate into endoderm-like cells by retinoic acid treatment. We analyzed the function of several regulatory factors of transcription and DNA replication in relation to the F9 cell differentiation.1. The enhancer of a mutant of polyomavirus, F9-5000, had a 24bp deletion and could function in F9 cells as well as in those induced to differentiate by retinoic acid. The DELTAF9-5000 element corresponds to the deleted region of the enhancer. This element functioned to suppress gene expression in F9 cells and bound a factor, PEBP4, which was thought to be responsible for the repression. In differentiated cells, however, the same element enhanced gene expression and bound transcriptional activator, PEBP2, as well as PEBP4. The recognition sequence of PEBP2 partly overlapped with that of PEBP4. PEBP3 (dephosphorylated form of PEBP2) and PFBP4 were actually shown to compete for the site for binding. Interplay of a ubiquitous negative factor and differentiation-induced positive factor may represent one aspect of the gene regulation during embryonic development.2. A transcriptional activator, AP1, is a heterodimer of the products of nuclear proto-oncogenes, c-jun and c-fos and is undetectable in F9 cells. The activated c-Ha-ras oncogene was found to induce the AP1 activity in F9 cells. This induction appeared to be due to the induction of c-jun gene transcription. Both the activated c-Ha-ras and c-jun genes induced the differentiation of F9 cells to endoderm-like cells.AP1 appeared to play a key role at the initial stage of the Fg cell differentiation.