The E2F transcription factor activates a replication-dependent human H2A gene in early S phase of the cell cycle.

Histone gene expression is restricted to the S phase of the cell cycle. Control is mediated by a complex network of sequence-specific DNA-binding factors and protein-protein interactions in response to cell cycle progression. To further investigate the regulatory functions that are associated at the transcriptional level, we analyzed the regulation of a replication-dependent human H2A.1-H2B.2 gene pair. We found that transcription factor E2F binds specifically to an E2F recognition motif in the H2A.1 promoter region. Activation of the H2A.1 promoter by E2F-1 was shown by use of luciferase reporter constructs of the intergenic promoter region. Overexpression of the human retinoblastoma suppressor gene product RB suppressed E2F-1 mediated transcriptional activation, indicating an E2F-dependent regulation of promoter activity during the G1-to-S-phase transition. Furthermore, the activity of the H2A.1 promoter was also downregulated by overexpression of the RB-related p107, a protein that has been detected in S-phase-specific protein complexes of cyclin A, E2F, and cdk2. In synchronized HeLa cells, expression of luciferase activity was induced at the beginning of DNA synthesis and was dependent on the presence of an E2F-binding site in the H2A.1 promoter. Together with the finding that E2F-binding motifs are highly conserved in H2A promoters of other species, our results suggest that E2F plays an important role in the coordinate regulation of S-phase-specific histone gene expression.

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Role for a YY1-Binding Element in Replication-Dependent Mouse Histone Gene Expression

Molecular and Cellular Biology ◽

10.1128/mcb.18.12.7106 ◽

1998 ◽

Vol 18 (12) ◽

pp. 7106-7118 ◽

Cited By ~ 38

Author(s):

Katherine A. Eliassen ◽

Amy Baldwin ◽

Eric M. Sikorski ◽

Myra M. Hurt

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Transcription Factor ◽

Protein Interaction ◽

Histone Gene ◽

Cycle Phase ◽

Histone Gene Expression ◽

Dna Protein Interaction

ABSTRACT Expression of the highly conserved replication-dependent histone gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated α, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 α element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 α sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro histone α DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone α DNA-YY1 interaction alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo. Because all mutations or deletions of the histone α sequence both abolish interactions in vitro and cause an in vivo decrease in histone gene expression, the recognition of the histone α element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.

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The control of histone gene expression

Biochemical Society Transactions ◽

10.1042/bst20120065 ◽

2012 ◽

Vol 40 (4) ◽

pp. 880-885 ◽

Cited By ~ 40

Author(s):

Alexander M.J. Rattray ◽

Berndt Müller

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Dna Replication ◽

Histone Gene ◽

Transcriptional Level ◽

Control Mechanisms ◽

Histone Proteins ◽

Histone Gene Expression ◽

Replication Control

Histone proteins are essential for the packaging of DNA into chromosomes. Histone gene expression is cell-cycle-regulated and coupled to DNA replication. Control of histone gene expression occurs at the transcriptional and post-transcriptional level and ensures that a fine balance between histone abundance and DNA replication is maintained for the correct packaging of newly replicated DNA into chromosomes. In the present paper, we review histone gene expression, highlighting the control mechanisms and key molecules involved in this process.

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Distinct replication-independent and -dependent phases of histone gene expression during the Physarum cell cycle.

Molecular and Cellular Biology ◽

10.1128/mcb.7.5.1933 ◽

1987 ◽

Vol 7 (5) ◽

pp. 1933-1937 ◽

Cited By ~ 5

Author(s):

J J Carrino ◽

V Kueng ◽

R Braun ◽

T G Laffler

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Dna Replication ◽

Dna Synthesis ◽

S Phase ◽

Histone Gene ◽

Histone Mrna ◽

Histone Gene Expression ◽

Tightly Coupled ◽

G2 Phase

During the S phase of the cell cycle, histone gene expression and DNA replication are tightly coupled. In mitotically synchronous plasmodia of the myxomycete Physarum polycephalum, which has no G1 phase, histone mRNA synthesis begins in mid-G2 phase. Although histone gene transcription is activated in the absence of significant DNA synthesis, our data demonstrate that histone gene expression became tightly coupled to DNA replication once the S phase began. There was a transition from the replication-independent phase to the replication-dependent phase of histone gene expression. During the first phase, histone mRNA synthesis appears to be under direct cell cycle control; it was not coupled to DNA replication. This allowed a pool of histone mRNA to accumulate in late G2 phase, in anticipation of future demand. The second phase began at the end of mitosis, when the S phase began, and expression became homeostatically coupled to DNA replication. This homeostatic control required continuing protein synthesis, since cycloheximide uncoupled transcription from DNA synthesis. Nuclear run-on assays suggest that in P. polycephalum this coupling occurs at the level of transcription. While histone gene transcription appears to be directly switched on in mid-G2 phase and off at the end of the S phase by cell cycle regulators, only during the S phase was the level of transcription balanced with the rate of DNA synthesis.

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