The lysine demethylase KDM4A controls the cell-cycle expression of replicative canonical histone genes

Using a Saccharomyces cerevisiae strain containing an integrated copy of an H2A-lacZ fusion gene, we screened for mutants which overexpressed beta-galactosidase as a way to identify genes which regulate transcription of the histone genes. Five recessive mutants with this phenotype were shown to contain altered regulatory genes because they had lost repression of HTA1 transcription which occurs upon inhibition of chromosome replication (D. E. Lycan, M. A. Osley, and L. Hereford, Mol. Cell. Biol. 7:614-621, 1987). Periodic transcription was affected in the mutants as well, since the HTA1 gene was transcribed during the G1 and G2 phases of the cell cycle, periods in the cell cycle when this gene is normally not expressed. A similar loss of cell cycle-dependent transcription was noted for two of the three remaining histone loci, while the HO and CDC9 genes continued to be expressed periodically. Using isolated promoter elements inserted into a heterologous cycl-lacZ fusion gene, we demonstrated that the mutations fell in genes which acted through a negative site in the TRT1 H2A-H2B promoter.

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Cell cycle expression of histone genes in Trypanosoma cruzi

Molecular and Biochemical Parasitology ◽

10.1016/s0166-6851(01)00214-6 ◽

2001 ◽

Vol 113 (2) ◽

pp. 215-222 ◽

Cited By ~ 11

Author(s):

René F Recinos ◽

Louis V Kirchhoff ◽

John E Donelson

Keyword(s):

Cell Cycle ◽

Trypanosoma Cruzi ◽

Histone Genes

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Induction of yeast histone genes by stimulation of stationary-phase cells

Molecular and Cellular Biology ◽

10.1128/mcb.10.12.6356-6361.1990 ◽

1990 ◽

Vol 10 (12) ◽

pp. 6356-6361

Author(s):

M A Drebot ◽

L M Veinot-Drebot ◽

R A Singer ◽

G C Johnston

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Stationary Phase ◽

Mitotic Cell ◽

Specific Gene ◽

Mitotic Cell Cycle ◽

Histone Genes ◽

Yeast Saccharomyces Cerevisiae ◽

Alpha Factor ◽

Stimulation Of

In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that is unrelated to the mitotic cell cycle. Expression of histone genes, as assessed by Northern (RNA) analysis, was shown to increase promptly after the stimulation, brought about by fresh medium, that activates stationary-phase cells to reenter the mitotic cell cycle. The use of a yeast mutant that is conditionally blocked in the resumption of proliferation at a step that is not part of the mitotic cell cycle (M.A. Drebot, G.C. Johnston, and R.A. Singer, Proc. Natl. Acad. Sci. 84:7948, 1987) showed that this increased gene expression that occurs upon stimulation of stationary-phase cells took place in the absence of DNA synthesis and without the performance of start. This stimulation-specific gene expression was blocked by the mating pheromone alpha-factor, indicating that alpha-factor directly inhibits expression of these histone genes, independently of start.

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Role of transcriptional and posttranscriptional regulation in expression of histone genes in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.7.2.614-621.1987 ◽

1987 ◽

Vol 7 (2) ◽

pp. 614-621

Author(s):

D E Lycan ◽

M A Osley ◽

L M Hereford

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Dna Replication ◽

Posttranscriptional Regulation ◽

Cell Cycle Control ◽

Dimensional Structure ◽

Histone Genes ◽

Transcriptional Regulatory Mechanisms ◽

Rna Levels

We analyzed the role of posttranscriptional mechanisms in the regulation of histone gene expression in Saccharomyces cerevisiae. The rapid drop in histone RNA levels associated with the inhibition of ongoing DNA replication was postulated to be due to posttranscriptional degradation of histone transcripts. However, in analyzing the sequences required for this response, we showed that the coupling of histone RNA levels to DNA replication was due mostly, if not entirely, to transcriptional regulatory mechanisms. Furthermore, deletions which removed the negative, cell cycle control sequences from the histone promoter also uncoupled histone transcription from DNA replication. We propose that the arrest of DNA synthesis prematurely activates the regulatory pathway used in the normal cell cycle to repress transcription. Although posttranscriptional regulation did not appear to play a significant role in coupling histone RNA levels to DNA replication, it did affect the levels of histone RNA in the cell cycle. Posttranscriptional regulation could apparently restore much of the periodicity of histone RNA accumulation in cells which constitutively transcribed the histone genes. Unlike transcriptional regulation, periodic posttranscriptional regulation appears to operate on a clock which is independent of events in the mitotic DNA cycle. Posttranscriptional recognition of histone RNA must require either sequences in the 3' end of the RNA or an intact three-dimensional structure since H2A- and H2B-lacZ fusion transcripts, containing only 5' histone sequences, were insensitive to posttranscriptional controls.

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