A positive role for histone acetylation in transcription factor access to nucleosomal DNA

Lee, Daniel Y.; Hayes, Jeffrey J.; Pruss, Dmitry; Wolffe, Alan P.

doi:10.1016/0092-8674(93)90051-q

Cited by 1,058 publications

(774 citation statements)

References 64 publications

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“…The kinetics of AN-9-induced histone acetylation were faster than those of butyrate. The histone hyperacetylation loosened the chromatin structure (Lee et al, 1993), and this may improve the accessibility of DNR to nucleosomal DNA. A reversible increase of histone acetylation by AN-9 and the requirement of simultaneous treatment with AN-9 and DNR are compatible with this view.…”

Section: Resultsmentioning

confidence: 99%

An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells

Kasukabe

Rephaeli²,

Honma³

1997

Br J Cancer

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Summary A derivative of butyric acid, pivalyloxymethyl butyrate , inhibited the proliferation and induced apoptosis of mouse monocytic leukaemia Mm-A cells, although sodium butyrate, but not AN-9, induced differentiation of the cells. AN-9 and DNA-specific antineoplastic agents synergistically inhibited the growth of Mm-A cells, and the simultaneous treatment was required to evoke the maximum growth-inhibitory effect. On the other hand, there was no synergy between butyrate and the drugs, or AN-9 and anti-metabolic agents in inhibiting the growth of the cells, suggesting that the synergistic effect is specific to AN-9 and DNA-reacting agents. AN-9 as a single agent prolonged the survival of mice inoculated with Mm-A cells in a dose-dependent manner. Moreover, administration of AN-9 plus daunorubicin (DNR) markedly prolonged their survival. These results suggest that combination with AN-9 and DNR entails an obvious therapeutic potential.

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Section: Resultsmentioning

confidence: 99%

An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells

Kasukabe

Rephaeli²,

Honma³

1997

Br J Cancer

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“…Because in previous research only post-transcriptional regulation of Pdx1 expression and function by ROS or antioxidant has been suggested [6,20,23,25], our finding on the hyperacetylation of H3 and H4 histone at the proximal promoter of Pdx1 in the OE mice reveals not only a novel, in vivo epigenetic, but also a potential transcriptional regulation for this key factor by antioxidant enzymes. Preceding transcriptional activation [43], hyperacetylation of H3 and H4 helps remodel the chromatin at Pdx1 promoter to form a more accessible structure for transcription [44]. This modification helps explain the increased Pdx1 mRNA levels in the OE islet and is strongly associated with the GPX1 function of H 2 O 2 degradation.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice

et al. 2008

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Aims/hypothesis We previously observed hyperglycaemia, hyperinsulinaemia, insulin resistance and obesity in Gpx1-overexpressing mice (OE). Here we determined whether these phenotypes were eliminated by diet restriction, subsequently testing whether hyperinsulinaemia was a primary effect of Gpx1 overexpression and caused by dysregulation of pancreatic duodenal homeobox 1 (PDX1) and uncoupling protein-2 (UCP2) in islets. Methods First, 24 male OE and wild-type (WT) mice (2 months old) were given 3 g (diet-restricted) or 5 g (fullfed) feed per day for 4 months to compare their glucose metabolism. Thereafter, several mechanistic experiments were conducted with pancreas and islets of the two genotypes (2 or 6 months old) to assay for beta cell mass, reactive oxygen species (ROS) levels, mitochondrial membrane potential (Δ= m ) and expression profiles of regulatory proteins. A functional assay of islets was also performed. Results Diet restriction eliminated obesity but not hyperinsulinaemia in OE mice. These mice had greater pancreatic beta cell mass (more than twofold) and pancreatic insulin content (40%) than the WT, along with an enhanced Δ= m and glucose-stimulated insulin secretion in islets. With diminished ROS production, the OE islets displayed hyperacetylation of H3 and H4 histone in the Pdx1 promoter, elevated PDX1 and decreased UCP2. Conclusions/interpretation Overproduction of the major antioxidant enzyme, glutathione peroxidase 1, caused seemingly beneficial changes in pancreatic PDX1 and UCP2, but eventually led to chronic hyperinsulinaemia by dysregulating islet insulin production and secretion.

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“…After the incubation of thymocytes in the absence or presence of packed into 30 nm chromatin fibers, the structure of chromathe compounds, the cells were collected and washed twice with phostin is seemed to prevent access of a variety of enzymes [2].…”

Section: Dna Fragmentationmentioning

confidence: 99%

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

et al. 1996

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A positive role for histone acetylation in transcription factor access to nucleosomal DNA

Cited by 1,058 publications

References 64 publications

An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells

An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells

Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice

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

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