High mobility group protein D


The midblastula transition in Xenopus

The the role of chromatin in activation of transcription during early development as well as the requirement for trans-acting factors during this period has been analysed in Xenopus. Basal transcription is repressed both during oogenesis and after the mid-blastula transition (MBT).  Transactivators are required to relieve this repression. In contrast, transactivators cannot overcome the generalized transcriptional repression that occurs in embryos before MBT. However, they do bind to promoters leading to a repressed but preset chromatin structure. Experiments involving the pre-binding of TATA binding protein (TBP) or of the strong transactivator GAL4-VP16 further show that there is no limiting factor before the MBT, and that it is the recruitment and stabilization of the basal transcription machinery and not of transactivators that is repressed during early development. This multi-step process in gene activation, with activation of promoters temporally uncoupled from their commitment, may be of importance in the regulation of early embryonic events by providing molecular signposts for future transcriptional processes (Prioleau, 1995).

Transcriptional quiescence of class II and class III genes prior to the mid-blastula transition (MBT) has been studied in Xenopus. An artificial increase in the amount of DNA present within the embryo, over the amount found at the MBT, allows precocious transcription of tRNA genes, but not of the adenovirus E4 or human cytomegalovirus (CMV) promoters. Thus titration of an inhibitor by exogenous DNA determines class III but not class II gene activation. The action of the inhibitor depends on the association of core histones with DNA. The addition of exogenous TBP, together with an increase in the amount of DNA within the embryo, allows significant basal transcription of class II genes prior to the MBT, whereas it does not increase transcription of tRNA genes. Precocious transcriptional activation of a defined minimal promoter containing five Gal4 binding sites and the activator Gal4-VP16 is directed by Gal4-VP16 prior to the MBT, demonstrating that a functional transcriptional machinery exists at this early developmental stage. Furthermore, since this activation can occur in the absence of exogenous TBP or chromatin titration, a transcription factor that can penetrate chromatin is sufficient for recruitment of this machinery to a promoter. These results support the hypothesis that the temporal regulation of transcription during early embryogenesis in Xenopus reflects not only a titration of inhibitors by DNA, but also a deficiency in the activity of transcriptional activators prior to the MBT (Almouzni, 1995).

Xenopus oocyte 5S RNA genes are normally activated at the mid-blastula transition and are subsequently repressed as gastrulation proceeds. The incorporation of histone H1 into chromatin during embryogenesis directs the specific repression of the Xenopus oocyte 5S rRNA genes before gastrulation is complete. The only genes known to be influenced by H1 protein are the oocyte 5s rRNA genes. An increase in histone H1 content specifically restricts TFIIIA-activated transcription;  a decrease in histone H1 within chromatin facilitates the activation of the oocyte 5S rRNA genes by TFIIIA. Variation in the amount of histone H1 in chromatin does not significantly influence somatic 5S rRNA gene transcription. Thus, the regulated expression of histone H1 during Xenopus development has a specific and dominant role in mediating the differential expression of the oocyte and somatic 5S rRNA genes. This demonstrates that histones can exert dominant repressive effects on the transcription of a gene in vivo in spite of an abundance of transcription factors for that gene (Bouvet, 1994b). Messenger RNA synthesized within the Xenopus oocyte nucleus is translated with an efficiency 50 times less than that of mRNA injected into the oocyte cytoplasm. For histone H1 mRNA this effect is independent of mRNA splicing, nuclear export, and the promoter driving transcription. The mRNA synthesized in vivo is translationally competent but is masked from the translational machinery in the cytoplasm through association with proteins including frog Y-box protein 2 (FRGY2). FRGY2, an RNA binding protein, associates with a broad spectrum of mRNAs exhibiting no apparent sequence specificity. FRGY2 has a general role in packaging mRNA in early Xenopus embryos. Overexpression of FRGY2 facilitates the translational repression of mRNA synthesized within Xenopus oocytes. The requirement for transcription to occur in vivo before a translationally repressed state can be established suggests that these two events are functionally coupled in Xenopus oocytes (Bouvet, 1994a).

High mobility group protein D: Biological Overview | Regulation | Developmental Biology | Effects of Mutation | References

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