Biosynthesis of Human Chorionic Gonadotropin*

505

429

We have analyzed the kinetics of accumulation of each of the individual core histone mRNAs throughout the HeLa cell cycle in cells synchronized by sequential thymidine and aphidicolin treatments. These analyses showed that during the S phase there was a 15-fold increase in the levels of histone mRNAs and that this resulted from both an increased rate of synthesis and a lengthening of the half-life of histone mRNAs. A comparison of the kinetics of accumulation of histone mRNA in the total cellular and nuclear RNA populations suggested an increased transcription rate through the S phase. Within 30 min after the inhibition of DNA synthesis in mid-S phase, the steady-state concentration and the rate of synthesis of histone mRNA each declined to their non-S-phase levels. Reactivation of histone mRNA accumulation could occur even after an extended mid-Sphase block in DNA synthesis. These results suggest that the mechanisms responsible for histone mRNA synthesis are not restricted to the Gl/S boundary of the HeLa cell cycle, but can operate whenever DNA synthesis is occurring.

Section: Resultsmentioning

confidence: 99%

Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle.

Heintz¹,

Sive²,

Roeder³

1983

505

429

“…However, it is unclear if this distinction reflects differences in the regulation of a gene expression in ectopic tumors as compared with eutopic placental cells. Various inhibitors of DNA synthesis are also reported to increase a protein levels in both ectopic (8,12,25) and eutopic (2,35,36,65) cells; further, eutopic placental cells have been shown to initially express a mRNA in development (34) in cytotrophoblasts as they fuse into a syncytial mass and exit the cell cycle (43,44,70). Because butyrate acts to inhibit DNA synthesis and cell cycle progression in ectopic tumors (16,21,28,40), yet is reported to have no effect on DNA synthesis in eutopic cells (10), the inhibition of DNA synthesis, or a related cell cycle phenomenon, has been suggested as a possible common mediator of a gene expression in both cell types.…”

Section: Discussionmentioning

confidence: 99%

Independent regulation by sodium butyrate of gonadotropin alpha gene expression and cell cycle progression in HeLa cells.

Darnell¹

1984

Sodium butyrate alters the growth and gene expression of a variety of differentiating and neoplastic cell types. For example, addition of 5 mM butyrate to HeLa cells is reported to both induce gonadotropin alpha subunit biosynthesis and block cell cycling in G1. We have studied these two actions of butyrate on HeLa cells and found that they are regulated in distinct ways. The induction of alpha subunit synthesis was due to an increase in the rate of transcription of the alpha gene. Using synchronized populations of HeLa cells, we determined that butyrate stimulates alpha transcription throughout the cell cycle. In contrast, treated cells arrest in G1 only if exposed to butyrate for a discrete period during the previous S phase. We conclude that butyrate inhibits DNA synthesis through a cell cycle-specific action that is independent from its direct action to stimulate transcription of the gonadotropin alpha gene.

“…In ectopic and eutopic cell lines, a expression appears to respond differently to cyclic AMP (cAMP) and sodium butyrate. For example, cAMP induces a protein synthesis in eutopic cell lines (7,(21)(22)(23), but has little or no effect on a protein levels in * Corresponding author. ectopic cells (21; unpublished data).…”

mentioning

confidence: 99%

Differential expression of the human gonadotropin alpha gene in ectopic and eutopic cells.

Darnell¹,

Boime²

1985