Effect of adenovirus infection on expression of human histone genes

The influence of adenovirus type 2 infection of HeLa cells upon expression of human histone genes was examined as a function of the period of infection. Histone RNA synthesis was assayed after run-off transcription in nuclei isolated from mock-infected cells and after various periods of adenovirus infection. Histone protein synthesis was measured by [3H]leucine labeling of intact cells and fluorography of electrophoretically fractionated nuclear and cytoplasmic proteins. The cellular representation of RNA species complementary to more than 13 different human histone genes was determined by RNA blot analysis of total cellular, nuclear or cytoplasmic RNA by using a series of 32P-labeled cloned human histone genes as hybridization probes and also by analysis of 3H-labeled histone mRNA species synthesized in intact cells. By 18 h after infection, HeLa cell DNA synthesis and all parameters of histone gene expression, including transcription and the nuclear and cytoplasmic concentrations of core and H1 mRNA species, were reduced to less than 5 to 10% of the control values. By contrast, transcription and processing of other cellular mRNA sequences have been shown to continue throughout this period of infection. The early period of adenovirus infection was marked by an inhibition of transcription of histone genes that accompanied the reduction in rate of HeLa cell DNA synthesis. These results suggest that the adenovirus-induced inhibition of histone gene expression is mediated in part at the transcriptional level. However, the persistence of histone mRNA species at concentrations comparable to those of mock-infected control cells during the early phase of the infection, despite a reduction in histone gene transcription and histone protein synthesis, implies that histone gene expression is also regulated post-transcriptionally in adenovirus-infected cells. These results suggest that the tight coupling between histone mRNA concentrations and the rate of cellular DNA synthesis, observed when DNA replication is inhibited by a variety of drugs, is not maintained after adenovirus infection.

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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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Drosophila Histone Locus Body assembly and function involves multiple interactions

10.1101/2020.03.16.994483 ◽

2020 ◽

Author(s):

Kaitlin P. Koreski ◽

Leila E. Rieder ◽

Lyndsey M. McLain ◽

William F. Marzluff ◽

Robert J. Duronio

Keyword(s):

Gene Expression ◽

Repeat Unit ◽

Gene Array ◽

Homozygous Deletion ◽

Histone Gene ◽

Histone Genes ◽

Histone Mrna ◽

Histone Gene Expression ◽

Histone Locus Body ◽

Histone Locus

AbstractThe histone locus body (HLB) assembles at replication-dependent (RD) histone loci and concentrates factors required for RD histone mRNA biosynthesis. The D. melanogaster genome has a single locus comprised of ∼100 copies of a tandemly arrayed repeat unit containing one copy of each of the 5 RD histone genes. To determine sequence elements required for D. melanogaster HLB formation and histone gene expression, we used transgenic gene arrays containing 12 copies of the histone repeat unit that functionally complement loss of the ∼200 endogenous RD histone genes. A 12x histone gene array in which all H3-H4 promoters were replaced with H2a-H2b promoters does not form an HLB or express high levels of RD histone mRNA in the presence of the endogenous histone genes. In contrast, this same transgenic array is active in HLB assembly and RD histone gene expression in the absence of the endogenous RD histone genes and rescues the lethality caused by homozygous deletion of the RD histone locus. The HLB formed in the absence of endogenous RD histone genes on the mutant 12x array contains all known factors present in the wild type HLB including CLAMP, which normally binds to GAGA repeats in the H3-H4 promoter. These data suggest that multiple protein-protein and/or protein-DNA interactions contribute to HLB formation, and that the large number of endogenous RD histone gene copies sequester available factor(s) from attenuated transgenic arrays, thereby preventing HLB formation and gene expression.

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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.7.5.1933-1937.1987 ◽

1987 ◽

Vol 7 (5) ◽

pp. 1933-1937

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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Histone gene expression in human diploid fibroblasts: analysis of histone mRNA levels using cloned human histone genes

Molecular and Cellular Biochemistry ◽

10.1007/bf00222482 ◽

1984 ◽

Vol 60 (2) ◽

Cited By ~ 6

Author(s):

L. Green ◽

G. Stein ◽

J. Stein

Keyword(s):

Gene Expression ◽

Histone Gene ◽

Mrna Levels ◽

Histone Genes ◽

Histone Mrna ◽

Diploid Fibroblasts ◽

Human Diploid Fibroblasts ◽

Histone Gene Expression

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Super resolution light microscopy of the Drosophila Histone Locus Body reveals a core-shell organization associated with expression of replication dependent histone genes

Molecular Biology of the Cell ◽

10.1091/mbc.e20-10-0645 ◽

2021 ◽

pp. mbc.E20-10-0645

Author(s):

James P. Kemp ◽

Xiao-Cui Yang ◽

Zbigniew Dominski ◽

William F. Marzluff ◽

Robert J. Duronio

Keyword(s):

Gene Expression ◽

Gene Transcription ◽

Nuclear Body ◽

Histone Gene ◽

Core Shell ◽

Histone Genes ◽

The Core ◽

Histone Gene Expression ◽

Histone Locus ◽

Histone Gene Transcription

The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of replication-dependent (RD) histone mRNAs, which are the only eukaryotic mRNAs lacking a poly-A tail. Many nuclear bodies contain distinct domains, but how internal organization is related to nuclear body function is not fully understood. Here, we demonstrate using structured illumination microscopy that Drosophila HLBs have a “core-shell” organization in which the internal core contains transcriptionally active RD histone genes. The N-terminus of Mxc, which contains a domain required for Mxc oligomerization, HLB assembly, and RD histone gene expression, is enriched in the HLB core. In contrast, the C-terminus of Mxc is enriched in the HLB outer shell as is FLASH, a component of the active U7 snRNP that co-transcriptionally cleaves RD histone pre-mRNA. Consistent with these results, we show biochemically that FLASH binds directly to the Mxc C-terminal region. In the rapid S-M nuclear cycles of syncytial blastoderm Drosophila embryos, the HLB disassembles at mitosis and reassembles the core-shell arrangement as histone gene transcription is activated immediately after mitosis. Thus, the core-shell organization is coupled to zygotic histone gene transcription, revealing a link between HLB internal organization and RD histone gene expression.

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The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells

Journal of Cell Science ◽

10.1242/jcs.01523 ◽

2004 ◽

Vol 117 (25) ◽

pp. 6043-6051 ◽

Cited By ~ 43

Author(s):

X. Zhao

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cell Proliferation ◽

Dna Synthesis ◽

Cell Cycle Progression ◽

Histone Gene ◽

Cycle Progression ◽

Histone Gene Expression ◽

Mitotic Cells

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Histone gene expression remains coupled to DNA synthesis during in vitro cellular senescence

Experimental Cell Research ◽

10.1016/0014-4827(87)90397-1 ◽

1987 ◽

Vol 172 (2) ◽

pp. 397-403 ◽

Cited By ~ 8

Author(s):

Gerard Zambetti ◽

Robert Dell'Orco ◽

Gary Stein ◽

Janet Stein

Keyword(s):

Gene Expression ◽

Dna Synthesis ◽

Cellular Senescence ◽

Histone Gene ◽

Histone Gene Expression

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Monocistronic transcription is the physiological mechanism of sea urchin embryonic histone gene expression.

Molecular and Cellular Biology ◽

10.1128/mcb.1.7.661 ◽

1981 ◽

Vol 1 (7) ◽

pp. 661-671 ◽

Cited By ~ 11

Author(s):

A Mauron ◽

S Levy ◽

G Childs ◽

L Kedes

Keyword(s):

Gene Expression ◽

Steady State ◽

Early Development ◽

Sea Urchin ◽

Dna Sequences ◽

Messenger Rna ◽

Physiological Mechanism ◽

Histone Gene ◽

Histone Genes ◽

Histone Gene Expression

We have examined histone gene expression during the early stages of sea urchin embryogenesis. The five histone genes expressed at that time are contained in tandem repetitive segments. It has been suggested that adjacent coding regions and their intervening spacer sequences are transcribed into large polycistronic messenger ribonucleic acid (RNA) precursors. We have subcloned into pBR322 deoxyribonucleic acid (DNA) sequences mapping either in the coding region, the 5' spacer, or the 3' spacer of the H2B histone gene. These clones were used to produce radioiodinated hybridization probes. We measured the steady-state quantity of H2B messenger RNA as well as spacer-specific RNA in the total RNA from embryos taken at various stages of development from fertilization to hatching of blastulae (0 to 22 h post-fertilization). Small amounts of RNA hybridizing to both spacer probes could be found. However, we show that these RNAs form mismatched hybrids with the spacer DNA and therefore cannot originate from the spacers present in the histone genes. We conclude that there is no detectable transcription of the spacer regions on either side of the H2B histone gene. The detection limit for RNA complementary to the 5' spacer sequence corresponds to a maximum of about three RNA molecules per cell, an amount shown to be far less than the projected steady-state pool size of a putative polycistronic transcript, if such a precursor were to be the obligatory transcript of the histone genes. (This conclusion was derived by using the known rates of production of H2B mRNA throughout early development [R. E. Maxson and F. H. Wilt, Dev. Biol., in press].) The physiologically relevant transcript of the histone genes in early development is therefore monocistronic and probably identical to the messenger RNA itself.

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