Modification of Histones by Sugar β-N-Acetylglucosamine (GlcNAc) Occurs on Multiple Residues, Including Histone H3 Serine 10, and Is Cell Cycle-regulated

The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription and cell division cycle control. Deletion and linker disruption mutations identified two classes of regulatory elements: multiple cell cycle activation (CCA) sites and a negative regulatory site (NRS). Duplicate 19-bp CCA sites are present in both the copy I and copy II histone H3-H4 promoters arranged as inverted repeats separated by 45 and 68 bp. The CCA sites are both necessary and sufficient to activate transcription under cell division cycle control. A single CCA site provides cell cycle control but is a weak transcriptional activator, while an inverted repeat comprising two CCA sites provides both strong transcriptional activation and cell division cycle control. The NRS was identified in the copy I histone H3-H4 promoter. Deletion or disruption of the NRS increased the level of the histone H3 promoter activity but did not alter the cell division cycle periodicity of transcription. When the CCA sites were deleted from the histone promoter, the NRS element was unable to confer cell division cycle control on the remaining basal level of transcription. When the NRS element was inserted into the promoter of a foreign reporter gene, transcription was constitutively repressed and did not acquire cell cycle regulation.

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Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum.

Molecular and Cellular Biology ◽

10.1128/mcb.5.11.2936 ◽

1985 ◽

Vol 5 (11) ◽

pp. 2936-2942 ◽

Cited By ~ 52

Author(s):

H T Liu ◽

R Baserga ◽

W E Mercer

Keyword(s):

Cell Cycle ◽

Dna Synthesis ◽

Thymidine Kinase ◽

Histone H3 ◽

Adenovirus Type ◽

3T3 Cells ◽

Cycle Dependent ◽

Cellular Dna ◽

Adenovirus Type 2

We have studied a panel of 10 genes and cDNA sequences that are expressed in a cell cycle-dependent manner in different types of cells from different species and that are inducible by different mitogens. These include five sequences (c-myc, 4F1, 2F1, 2A9, and KC-1) that are preferentially expressed in the early part of the G1 phase, three genes (ornithine decarboxylase, p53, and c-rasHa) preferentially expressed in middle or late G1, and two genes (thymidine kinase and histone H3) preferentially expressed in the S phase of the cell cycle. We have studied the expression of these genes in nonpermissive (tsAF8) and semipermissive (Swiss 3T3) cells infected with adenovirus type 2. Under the conditions of these experiments, adenovirus type 2 infection stimulates cellular DNA synthesis in both tsAF8 and 3T3 cells. However, four of the five early G1 genes (c-myc, 4F1, KC-1, and 2A9) and one of the late G1 genes (c-ras) are not induced by adenovirus infection, although they are strongly induced by serum. The other sequences (2F1, ornithine decarboxylase, p53, thymidine kinase, and histone H3) are activated by both adenovirus and serum. We conclude that the cell cycle-dependent genes activated by adenovirus 2 are a subset of the cell cycle-dependent genes activated by serum. The data suggest that the mechanisms by which serum and adenovirus induce cellular DNA synthesis are not identical.

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Depletion of KNL2 Results in Altered Expression of Genes Involved in Regulation of the Cell Cycle, Transcription, and Development in Arabidopsis

International Journal of Molecular Sciences ◽

10.3390/ijms20225726 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5726 ◽

Cited By ~ 1

Author(s):

Anastassia Boudichevskaia ◽

Andreas Houben ◽

Anne Fiebig ◽

Klara Prochazkova ◽

Ales Pecinka ◽

...

Keyword(s):

Cell Cycle ◽

Critical Role ◽

Histone H3 ◽

Global Gene Expression ◽

Proper Function ◽

Knockout Mutant ◽

Flower Bud ◽

Altered Expression ◽

Expression Of Genes ◽

Histone H3 Variant

Centromeres contain specialized nucleosomes at which histone H3 is partially replaced by the centromeric histone H3 variant cenH3 that is required for the assembly, maintenance, and proper function of kinetochores during mitotic and meiotic divisions. Previously, we identified a KINETOCHORE NULL 2 (KNL2) of Arabidopsis thaliana that is involved in the licensing of centromeres for the cenH3 recruitment. We also demonstrated that a knockout mutant for KNL2 shows mitotic and meiotic defects, slower development, reduced growth rate, and fertility. To analyze an effect of KNL2 mutation on global gene transcription of Arabidopsis, we performed RNA-sequencing experiments using seedling and flower bud tissues of knl2 and wild-type plants. The transcriptome data analysis revealed a high number of differentially expressed genes (DEGs) in knl2 plants. The set was enriched in genes involved in the regulation of the cell cycle, transcription, development, and DNA damage repair. In addition to comprehensive information regarding the effects of KNL2 mutation on the global gene expression, physiological changes in plants are also presented, which provides an integrated understanding of the critical role played by KNL2 in plant growth and development.

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Imaging the fate of histone Cse4 reveals de novo replacement in S phase and subsequent stable residence at centromeres

eLife ◽

10.7554/elife.02203 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 59

Author(s):

Jan Wisniewski ◽

Bassam Hajj ◽

Jiji Chen ◽

Gaku Mizuguchi ◽

Hua Xiao ◽

...

Keyword(s):

Cell Cycle ◽

Elevated Temperatures ◽

De Novo ◽

Histone H3 ◽

S Phase ◽

Nuclear Accumulation ◽

Histone H3 Variant ◽

Functionally Impaired ◽

Cell Cycle Dynamics ◽

Cell Lethality

The budding yeast centromere contains Cse4, a specialized histone H3 variant. Fluorescence pulse-chase analysis of an internally tagged Cse4 reveals that it is replaced with newly synthesized molecules in S phase, remaining stably associated with centromeres thereafter. In contrast, C-terminally-tagged Cse4 is functionally impaired, showing slow cell growth, cell lethality at elevated temperatures, and extra-centromeric nuclear accumulation. Recent studies using such strains gave conflicting findings regarding the centromeric abundance and cell cycle dynamics of Cse4. Our findings indicate that internally tagged Cse4 is a better reporter of the biology of this histone variant. Furthermore, the size of centromeric Cse4 clusters was precisely mapped with a new 3D-PALM method, revealing substantial compaction during anaphase. Cse4-specific chaperone Scm3 displays steady-state, stoichiometric co-localization with Cse4 at centromeres throughout the cell cycle, while undergoing exchange with a nuclear pool. These findings suggest that a stable Cse4 nucleosome is maintained by dynamic chaperone-in-residence Scm3.

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Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice

10.1101/2021.11.23.469796 ◽

2021 ◽

Author(s):

Yuting Liu ◽

Kehui Wang ◽

Li Huang ◽

Jicheng Zhao ◽

Xinpeng Chen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Viability ◽

Histone H3 ◽

Dependent Manner ◽

Centromere Function ◽

Histone H3 Variant ◽

A Cell ◽

Cycle Dependent ◽

Spatiotemporal Control

Centromere identity is defined by nucleosomes containing CENP-A, a histone H3 variant. The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner. We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68. However, a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading. Here, we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability. We also find that mice harboring the corresponding mutations are lethal. Together, these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.

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Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum

Molecular and Cellular Biology ◽

10.1128/mcb.5.11.2936-2942.1985 ◽

1985 ◽

Vol 5 (11) ◽

pp. 2936-2942

Author(s):

H T Liu ◽

R Baserga ◽

W E Mercer

Keyword(s):

Cell Cycle ◽

Dna Synthesis ◽

Thymidine Kinase ◽

Histone H3 ◽

Adenovirus Type ◽

3T3 Cells ◽

Cycle Dependent ◽

Cellular Dna ◽

Adenovirus Type 2

We have studied a panel of 10 genes and cDNA sequences that are expressed in a cell cycle-dependent manner in different types of cells from different species and that are inducible by different mitogens. These include five sequences (c-myc, 4F1, 2F1, 2A9, and KC-1) that are preferentially expressed in the early part of the G1 phase, three genes (ornithine decarboxylase, p53, and c-rasHa) preferentially expressed in middle or late G1, and two genes (thymidine kinase and histone H3) preferentially expressed in the S phase of the cell cycle. We have studied the expression of these genes in nonpermissive (tsAF8) and semipermissive (Swiss 3T3) cells infected with adenovirus type 2. Under the conditions of these experiments, adenovirus type 2 infection stimulates cellular DNA synthesis in both tsAF8 and 3T3 cells. However, four of the five early G1 genes (c-myc, 4F1, KC-1, and 2A9) and one of the late G1 genes (c-ras) are not induced by adenovirus infection, although they are strongly induced by serum. The other sequences (2F1, ornithine decarboxylase, p53, thymidine kinase, and histone H3) are activated by both adenovirus and serum. We conclude that the cell cycle-dependent genes activated by adenovirus 2 are a subset of the cell cycle-dependent genes activated by serum. The data suggest that the mechanisms by which serum and adenovirus induce cellular DNA synthesis are not identical.

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Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave

Nucleic Acids Research ◽

10.1093/nar/gkz561 ◽

2019 ◽

Vol 47 (16) ◽

pp. 8439-8451 ◽

Cited By ~ 1

Author(s):

Alberto González-Medina ◽

Elena Hidalgo ◽

José Ayté

Keyword(s):

Cell Cycle ◽

Molecular Mechanisms ◽

Histone H3 ◽

Dependent Manner ◽

Saga Complex ◽

Lysine Residues ◽

Physical Barriers ◽

A Cell ◽

Cycle Dependent ◽

Regulated Promoters

Abstract In fission yeast, MBF-dependent transcription is inactivated at the end of S phase through a negative feedback loop that involves the co-repressors, Yox1 and Nrm1. Although this repression system is well known, the molecular mechanisms involved in MBF activation remain largely unknown. Compacted chromatin constitutes a barrier to activators accessing promoters. Here, we show that chromatin regulation plays a key role in activating MBF-dependent transcription. Gcn5, a part of the SAGA complex, binds to MBF-regulated promoters through the MBF co-activator Rep2 in a cell cycle-dependent manner and in a reverse correlation to the binding of the MBF co-repressors, Nrm1 or Yox1. We propose that the co-repressors function as physical barriers to SAGA recruitment onto MBF promoters. We also show that Gcn5 acetylates specific lysine residues on histone H3 in a cell cycle-regulated manner. Furthermore, either in a gcn5 mutant or in a strain in which histone H3 is kept in an unacetylated form, MBF-dependent transcription is downregulated. In summary, Gcn5 is required for the full activation and correct timing of MBF-regulated gene transcription.

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