Phosphorylation of distinct regions of f1 histone. Relationship to the cell cycle.

Hohmann, Philip; Tobey, Robert A.; Gurley, L.R.

doi:10.1016/s0021-9258(17)33398-7

Cited by 133 publications

(43 citation statements)

References 35 publications

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“…During mitosis, histone H1 has been shown to have maximal phosphorylation. − To identify if our methodology is able to detect additional phosphorylation sites, we expanded database searches of the FT/FT LC-MS/MS data for other sites of H1 phosphorylation. Both phosphopeptide enrichment and shotgun proteomic strategies for histone H1 were able to identify several other histone H1.2 and H1.4 phosphorylation sites (Figure C).…”

Section: Resultsmentioning

confidence: 99%

“…Of these sites, the pT146 antisera are commercially available and validated for many applications. ,,,, Therefore, the pT146 site on histone H1 was selected for further validation in breast cancer. Phosphorylation of histone H1 has been shown to progressively increase as cells advance through the cell cycle. − Although others have described specific histone H1 phosphorylation sites as interphase and/or mitotic through blocking experiments, we sought to monitor the specific phosphorylation site pT146 on histone H1 across the entire cell cycle. ,,, Using MDA-MB-231 cells as a model cell line due to the high histone H1 phosphorylation content (Figure ), we conducted cell synchronization experiments as originally described by Bostock et al to monitor H1 phosphorylation . Figure B shows the change in DNA content by detecting propidium iodide fluorescent intensity using flow cytometry following cell synchronization.…”

Section: Resultsmentioning

confidence: 99%

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Histone H1 Phosphorylation in Breast Cancer

et al. 2014

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Breast cancer is the second leading cause of cancer-related deaths in women. The need for new clinical biomarkers in breast cancer is necessary to further predict prognosis and therapeutic response. In this article, the LC-MS histone H1 phosphorylation profiles were established for three distinct breast cancer cell lines. The results show that the extent of H1 phosphorylation can distinguish between the different cell lines. The histone H1 from the metastatic cell line, MDA-MB-231, was subjected to chemical derivitization and LC-MS/MS analysis. The results suggest that the phosphorylation at threonine 146 is found on both histone H1.2 and histone H1.4. Cell lines were then treated with an extracellular stimulus, estradiol or kinase inhibitor LY294002, to monitor changes in histone H1 phosphorylation. The data show that histone H1 phosphorylation can increase and decrease in response to extracellular stimuli. Finally, primary breast tissues were stained for the histone H1 phosphorylation at threonine 146. Variable staining patterns across tumor grades and subtypes were observed with pT146 labeling correlating with tumor grade. These results establish the potential for histone H1 phosphorylation at threonine 146 as a clinical biomarker in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Histone H1 Phosphorylation in Breast Cancer

et al. 2014

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“…In mammalian cells, there are zero to one phosphate per histone H1 during the G1 phase of the cell cy-cle, and this increases by another two phosphates during S phase. The level of phosphorylation then rises through G2 up to the hyperphosphorylated state of four to six phosphates per histone H1 at metaphase (17)(18)(19)21). This correlation between histone phosphorylation and chromosome condensation was also observed during the induction of premature chromosome condensation in sea urchin eggs and in mammalian cells (1,27).…”

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confidence: 74%

The topoisomerase II inhibitor VM-26 induces marked changes in histone H1 kinase activity, histones H1 and H3 phosphorylation, and chromosome condensation in G2 phase and mitotic BHK cells.

Roberge

Th'ng

Hamaguchi

et al. 1990

The Journal of Cell Biology

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Abstract. We have examined the effects of topoisomerase inhibitors on the phosphorylation of histones in chromatin during the G2 and the M phases of the cell cycle. Throughout the G2 phase of BHK cells, addition of the topoisomerase II inhibitor VM-26 prevented histone HI phosphorylation, accompanied by the inhibition of intraceUular histone H1 kinase activity. However, VM-26 had no inhibitory effect on the activity of the kinase in vitro, suggesting an indirect influence on histone H1 kinase activity. Entry into mitosis was also prevented, as monitored by the absence of nuclear lamina depolymerization, chromosome condensation, and histone H3 phosphorylation. In contrast, the topoisomerase I inhibitor, camptothecin, inhibited histone H1 phosphorylation and entry into mitosis only when applied at early G2.In cells that were arrested in mitosis, VM-26 induced dephosphorylation of histones H1 and H3, DNA breaks, and partial chromosome decondensation. These changes in chromatin parameters probably reverse the process of chromosome condensation, unfolding condensed regions to permit the repair of strand breaks in the DNA that were induced by VM-26. The involvement of growth-associated histone HI kinase in these processes raises the possibility that the cell detects breaks in the DNA through their effects on the state of DNA supercoiling in constrained domains or loops. It would appear that histone H1 kinase and topoisomerase II work coordinately in both chromosome condensation and decondensation, and that this process participates in the VM-26-induced G2 arrest of the cell.

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“…Although early studies of HI phosphorylation in hamster cells indicated that particular sites within H1 were phosphorylated at specific times during the cell cycle (Gurley et al, , 1978aHohmann et al, 1975Hohmann et al, , 1976), more recent studies in other cell types indicate that the order of phosphorylation-site use is not generally progessive (Hohmann, 1983). Instead, the proportion of phosphorylated molecules together with the number of phosphates per molecule change during the cell cycle (Ajiro et al, 1981a(Ajiro et al, ,b, 1983Langan, 1982) similar to the changes we have observed in this paper under different physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…H1 is highly phosphorylated in a number of different cell types, ranging from protozoa to mammals (for review see Hohmann, 1983). Both the level and specific sites of phosphorylation have been observed to change in response to development (Billings et al, 1979;Blumenfeld et al, 1978;Green and Poccia, 1985;Lennox et al, 1982;Newrock et al, 1978;Talmadge and Blumenfeld, 1987) or the progression of the cell cycle (Ajiro et al, 1981a(Ajiro et al, ,b, 1983Balhorn et al, 1972;Bradbury et al, 1974a,b;Gurley et al, 1975Gurley et al, , 1978aHohmann et al, 1975Hohmann et al, , 1976Langan, 1982;Y nox and Cohen, 1983). Indeed, a hyperphosphorylation ot rll during mitosis in higher eukaryotes has led to the correlation of such phosphorylation with the condensation of mitotic chromosomes (Balhorn et al, 1972;Bradbury et al, 1974a,b;Gurley et al, 1975Gurley et al, , 1978aInglis et al, 1976;Krystal and Poccia, 1981;Lake et al, 1972;Matsumoto et al, 1980;Paulson and Taylor, 1982;Tanphaichitr et al, 1976).…”

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confidence: 99%

Characterization of phosphorylation sites in histone H1 in the amitotic macronucleus of Tetrahymena during different physiological states.

Roth

Schulman

Richman

et al. 1988

The Journal of Cell Biology

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Abstract. Histone H1 is highly phosphorylated in transcriptionally active, amitotic macronuclei of Tetrahymena during vegetative growth. However, the level of H1 phosphorylation changes dramatically in response to different physiological conditions. H1 is hyperphosphorylated in response to heat shock and during prezygotic stages of conjugation. Conversely, H1 is largely dephosphorylated during prolonged starvation and during elimination of parental macronuclei during conjugation. Mapping of phosphorylation sites within HI indicates that phosphorylation occurs at multiple sites in the amino-terminal portion of the molecule, predominantly at threonine residues. Two of these sites have been identified by compositional analyses and microsequencing of tryptic peptides. Interestingly, two major sites contain the sequence Thr-ProVal-Lys similar to that contained in the sites recognized by growth-associated histone kinase in other organisms. No new sites are detected during the hyperphosphorylation of H1 which occurs during heat shock or in early stages of conjugation, and no sites are preferentially dephosphorylated during starvation or later stages of conjugation. Therefore, changes in the overall level of H1 phosphorylation, as opposed to phosphorylation or dephosphorylation at particular sites, appear to be important in the regulation of chromatin structure under these physiological conditions. Further, since no cell division or DNA replication occurs under these conditions, changes in the level of H1 phosphorylation are best correlated to changes in gene expression during heat shock, starvation, and conjugation. We suggest that, at least in Tetrahymena, H1 hyperphosphorylation is used as a rapid and transient mechanism for the cessation of transcription under conditions of cellular stress.

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Phosphorylation of distinct regions of f1 histone. Relationship to the cell cycle.

Cited by 133 publications

References 35 publications

Histone H1 Phosphorylation in Breast Cancer

Histone H1 Phosphorylation in Breast Cancer

The topoisomerase II inhibitor VM-26 induces marked changes in histone H1 kinase activity, histones H1 and H3 phosphorylation, and chromosome condensation in G2 phase and mitotic BHK cells.

Characterization of phosphorylation sites in histone H1 in the amitotic macronucleus of Tetrahymena during different physiological states.

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