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Cell cycle-related accumulation of H1(0) mRNA: induction in murine erythroleukemia cells
D Grunwald1, S Khochbin, J J Lawrence
1Unité Inserm 309, Département de Biologie Moléculaire et Structurale, Centre d'Etudes Nucléaires de Grenoble, France.
Abstract:
H1(0), a member of histone H1 family, is associated with cell differentiation in vivo and in vitro. Unlike other histones its synthesis is known to be constitutive during the cell cycle. The present paper provides evidence showing that, in murine erythroleukemia (MEL) cells, H1(0) mRNA accumulation is coupled to DNA replication, but this mRNA is stable enough to remain present all over the cell cycle. Moreover the experiments suggest that H1(0) mRNA accumulates in mid or late S phase rather than when cells initiate DNA replication as does H3 mRNA. H1(0) gene transcription is drastically induced by chemical inducers of differentiation in this cell line. In an attempt to better understand the mechanism of this process, we have studied the inducibility of this gene with respect to the position of the cells in the cell cycle. The experiments show that the most efficient accumulation of H1(0) is observed when cells are treated by the inducer during the S phase of the cell cycle. In the same conditions, H3 mRNA accumulation remains unaffected. These results show that H1(0) mRNA, like H3 mRNA, accumulates during DNA replication, although at a different stage in this phase. The two genes differ, however, in their response to the inducer, suggesting that different regulatory elements might be involved in such a response.
Insights
Histone H1(0) mRNA accumulation is linked to DNA replication in murine erythroleukemia cells. Its gene transcription is induced by differentiation chemicals, particularly during the S phase, unlike H3 mRNA.
Area of Science:
- Molecular Biology
- Cell Biology
- Epigenetics
Background:
- Histone H1(0) is a key protein in cell differentiation.
- Unlike other histones, H1(0) synthesis is typically constitutive throughout the cell cycle.
- Understanding H1(0) regulation is crucial for comprehending differentiation processes.
Purpose of the Study:
- To investigate the cell cycle regulation of H1(0) mRNA accumulation.
- To determine the impact of differentiation inducers on H1(0) gene transcription during specific cell cycle phases.
- To compare the regulatory mechanisms of H1(0) and H3 mRNA during cell differentiation.
Main Methods:
- Analysis of H1(0) mRNA accumulation in murine erythroleukemia (MEL) cells.
- Studying the effect of chemical inducers on H1(0) gene transcription.
- Cell cycle synchronization and treatment during specific phases (S phase).
- Comparative analysis with H3 mRNA expression patterns.
Main Results:
- H1(0) mRNA accumulation is coupled to DNA replication, occurring in mid or late S phase.
- H1(0) gene transcription is significantly induced by chemical differentiation inducers.
- The most efficient H1(0) accumulation occurs when inducers are applied during the S phase.
- H3 mRNA accumulation is unaffected by inducers under the same S phase treatment conditions.
Conclusions:
- H1(0) mRNA accumulation is regulated by DNA replication, with distinct timing compared to H3 mRNA.
- The inducibility of H1(0) by differentiation agents is cell cycle-dependent, specifically during S phase.
- Differential regulatory elements likely control the distinct responses of H1(0) and H3 genes to differentiation inducers.