Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosis

Lee, Eibai; Furukubo, Taku; Miyabe, Takashi; Yamauchi, Aiko; Kariya, Kimio

doi:10.1016/0014-5793(96)01033-2

Cited by 52 publications

(41 citation statements)

References 25 publications

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“…In addition, TSA led to extensive apoptosis in P19 cells. This and the recent report that TSA causes rapid apoptosis in rat thymocytes (35) suggest an intriguing possibility that histone acetylation has a role in programmed cell death. TSA-induced cell death in P19 cells, however, was offset by addition of RA, although RA itself caused moderate apoptosis (Fig.…”

Section: Discussionmentioning

confidence: 61%

A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells

Minucci

Horn

Bhattacharyya

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

104

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Histone acetylation is thought to have a role in transcription. To gain insight into the role of histone acetylation in retinoid-dependent transcription, we studied the effects of trichostatin A (TSA), a specific inhibitor of histone deacetylase, on P19 embryonal carcinoma cells. We show that coaddition of TSA and retinoic acid (RA) markedly enhances neuronal differentiation in these cells, although TSA alone does not induce differentiation but causes extensive apoptosis. Consistent with the cooperative effect of TSA and RA, coaddition of the two agents synergistically enhanced transcription from stably integrated RA-responsive promoters. The transcriptional synergy by TSA and RA required the RA-responsive element and a functional retinoid X receptor (RXR)͞retinoic acid receptor (RAR) heterodimer, both obligatory for RA-dependent transcription. Furthermore, TSA led to promoter activation by an RXR-selective ligand that was otherwise inactive in transcription. In addition, TSA enhanced transcription from a minimum basal promoter, independently of the RA-responsive element. Finally, we show that TSA alone or in combination with RA increases in vivo endonuclease sensitivity within the RA-responsive promoter, suggesting that TSA treatment might alter a local chromatin environment to enhance RXR͞RAR heterodimer action. Thus, these results indicate that histone acetylation inf luences activity of the heterodimer, which is in line with the observed interaction between the RXR͞RAR heterodimer and a histone acetylase presented elsewhere.

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Section: Discussionmentioning

confidence: 61%

A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells

Minucci

Horn

Bhattacharyya

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

104

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“…The isolated nuclei were prepared from rat thymocytes as described previously with minor modification (9). Briefly, thymocytes were incubated in the presence or absence of 5 nM calyculin A for 2 h, unless otherwise indicated.…”

Section: Methodsmentioning

confidence: 99%

“…Previously we demonstrated that inhibitors of histone deacetylase such as trichostatin A and sodium butyrate induced apoptosis in rat thymocytes (9). The hyperacetylation of histones preceded DNA fragmentation.…”

Section: Introductionmentioning

confidence: 92%

“…Because the packaging of the eukaryotic genome in chromatin restricts the access of the enzymes that process DNA (8), the only activation of CAD seems to be insufficient for the induction of DNA fragmentation in the nuclei. Therefore, it is necessary for the cleavage of chromosomal DNA during apoptosis to loosen the package of chromatin structure in the nuclei (9). However, little is known about the attempt to understand the molecular mechanism for DNA fragmentation of the cells undergoing apoptosis concerning the change in the structure of chromatin.…”

Section: Introductionmentioning

confidence: 99%

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Thymocyte Apoptosis Induced by Phosphorylation of Histones is Associated with the Change in Chromatin Structure to Allow Easy Accessibility of DNase

et al. 2002

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SummaryThe inhibitors of protein phosphatase such as calyculin A and okadaic acid induce the apoptotic cell death in rat thymocytes. To clarify the molecular mechanism of these inhibitor-induced apoptosis, the effect of calyculin A on DNA fragmentation in the isolated nuclei were studied. A significant increase in DNA fragmentation was observed in the nuclei prepared from the cells treated with calyculin A that caused histone hyperphosphorylation. No changes of the activities of caspase-8 and -3 were observed in the extract from the cells treated with calyculin A. The circular dichroism analysis of soluble chromatin from calyculin A-treated thymocyte nuclei indicated that phosphorylation of histones decreased its α-helical content. Thus, the change in the chromatin structure may be due to the chemical modification of histones. Moreover, the structural change in chromatin preceded DNA fragmentation in the nuclei. Therefore, these results suggest that the change of chromatin structure allow easy accessibility of nuclear DNase to chromosomal DNA. IUBMB Life, 54: 123-127, 2002

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“…51 The two T cell types investigated in the present study proved to be sensitive to apoptosis induction by dexamethasone as well as butyrate (or trichostatin A). It remains to be seen whether dexamethasone-sensitivity is always coupled with sensitivity to butyrate-(and trichostatin A)-induced apoptosis.…”

Section: Discussionmentioning

confidence: 59%

Interaction between dexamethasone and butyrate in apoptosis induction: non-additive in thymocytes and synergistic in a T cell-derived leukemia cell line

et al. 1999

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In thymocytes butyrate and trichostatin A are unable to augment dexamethasone-induced apoptosis. In cultured rat thymocytes the extent of apoptosis induced by dexamethasone alone did not increase by addition of 0.1 ± 10 mM butyrate. Even more pronounced was the non-additive interrelationship between dexamethasone and trichostatin A, as trichostatin A-induced apoptosis was not only blocked by the presence of dexamethasone but dexamethasoneinduced apoptosis was also partially inhibited in the presence of 0.1 ± 0.5 mM trichostatin A. The fact that the non-additive relationship with dexamethasone for apoptosis induction was observed with both histone deacetylase inhibitors suggests that in thymocytes this phenomenon is related to histone acetylation. In contrast to this, in the human T cell-derived leukemia cell line CEM-C7H2, dexamethasone did not block butyrate-or trichostatin A-induced apoptosis; moreover, butyrate, in the concentration range of 0.1 ± 1 mM, had a marked synergistic effect on dexamethasone-induced apoptosis. This synergism, however, was not mimicked by trichostatin A, indicating that the effect is not related to histone acetylation but rather due to a pleiotropic effect of butyrate. Furthermore, in CEM-C7H2 cells, at higher concentrations of butyrate (5 ± 10 mM) or trichostatin A (0.4 ± 0.8 mM), there was a minor but reproducible antagonistic effect of dexamethasone on apoptosis induced by each of the two histone deacetylase inhibitors, suggesting that this antagonistic effect too, is related to histone hyperacetylation.

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Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosis

Cited by 52 publications

References 25 publications

A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells

A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells

Thymocyte Apoptosis Induced by Phosphorylation of Histones is Associated with the Change in Chromatin Structure to Allow Easy Accessibility of DNase

Interaction between dexamethasone and butyrate in apoptosis induction: non-additive in thymocytes and synergistic in a T cell-derived leukemia cell line

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