Enhanced Histone Acetylation and Transcription: A Dynamic Perspective

Clayton, Alison L.; Hazzalin, Catherine A.; Mahadevan, Louis C.

doi:10.1016/j.molcel.2006.06.017

Cited by 421 publications

(360 citation statements)

References 76 publications

(95 reference statements)

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“…This overview of the published data and our own results suggest that there is a very early increase in global histone acetylation, whereas epigenetic events to restrict active chromatin including histone deacetylation, histone methylation, and DNA methylation dominate later time points. Histone acetylation is a dynamic process resulting from the balance between acetylase and deacetylase enzymes (35). We expect that the activity and targeting of these enzymes to specific loci will be affected by differentiation.…”

Section: Discussionmentioning

confidence: 99%

The Role of Histone Acetylation in Regulating Early Gene Expression Patterns during Early Embryonic Stem Cell Differentiation

McCool

Singer

et al. 2007

Journal of Biological Chemistry

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We have examined the role of histone acetylation in the very earliest steps of differentiation of mouse embryonic stem cells in response to withdrawal of leukemia inhibitory factor (LIF) as a differentiation signal. The cells undergo dramatic changes in morphology and an ordered program of gene expression changes representing differentiation to all three germ layers over the first 3-5 days of LIF withdrawal. We observed a global increase in acetylation on histone H4 and to a lesser extent on histone H3 over this time period. Treatment of the cells with trichostatin A (TSA), a histone deacetylase inhibitor, induced changes in morphology, gene expression, and histone acetylation that mimicked differentiation induced by withdrawal of LIF. We examined localized histone acetylation in the regulatory regions of genes that were transcriptionally either active in undifferentiated cells, induced during differentiation, or inactive under all treatments. There was striking concordance in the histone acetylation patterns of specific genes induced by both TSA and LIF withdrawal. Increased histone acetylation in local regions correlated best with induction of gene expression. Finally, TSA treatment did not support the maintenance or progression of differentiation. Upon removal of TSA, the cells reverted to the undifferentiated phenotype. We concluded that increased histone acetylation at specific genes played a role in their expression, but additional events are required for maintenance of differentiated gene expression and loss of the pluripotent state.

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Section: Discussionmentioning

confidence: 99%

The Role of Histone Acetylation in Regulating Early Gene Expression Patterns during Early Embryonic Stem Cell Differentiation

McCool

Singer

et al. 2007

Journal of Biological Chemistry

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“…Histone acetylation occurs at a lysine residue of histone tails and is modified by two opposing enzymes: histone acetyltransferases (HATs) 3 and histone deacetylases (HDACs) (10,11). An enhanced level of histone acetylation is generally correlated with accessible chromatin structure, which is seen not only in active gene transcription but also in nontranscribed genes poised for response (12). Furthermore, a decrease in histone acetylation using an inhibitor of HAT activity, such as curcumin, results in a decrease in gene expression (13).…”

Section: Histone Acetylation Facilitates Rapid and Robust Memory Cd8 mentioning

confidence: 99%

Histone Acetylation Facilitates Rapid and Robust Memory CD8 T Cell Response through Differential Expression of Effector Molecules (Eomesodermin and Its Targets: Perforin and Granzyme B)

Araki¹,

Fann²,

Wersto

et al. 2008

The Journal of Immunology

155

138

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To understand the mechanism regulating the effector function of memory CD8 T cells, we examined expression and chromatin state of a key transcription factor (eomesodermin, EOMES) and two of its targets: perforin (PRF1) and granzyme B (GZMB). Accessible chromatin associated histone 3 lysine 9 acetylation (H3K9Ac) was found significantly higher at the proximal promoter and the first exon region of all three genes in memory CD8 T cells than in naive CD8 T cells. Correspondingly, EOMES and PRF1 were constitutively higher expressed in memory CD8 T cells than in naive CD8 T cells at resting and activated states. In contrast, higher expression of GZMB was induced in memory CD8 T cells than in naive CD8 T cells only after activation. Regardless of their constitutive or inducible expression, decreased H3K9Ac levels after treatment with a histone acetyltransferase inhibitor (Curcumin) led to decreased expression of all three genes in activated memory CD8 T cells. These findings suggest that H3K9Ac associated accessible chromatin state serves as a corner stone for the differentially high expression of these effector genes in memory CD8 T cells. Thus, epigenetic changes mediated via histone acetylation may provide a chromatin “memory” for the rapid and robust transcriptional response of memory CD8 T cells.

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“…Exposure of cancer cells to HDAC inhibitors is associated with a multitude of molecular and biological effects, ranging from transcriptional control, chromatin plasticity, protein DNA interaction to cellular differentiation, growth arrest and apoptosis. HDAC inhibitors are an exciting new addition to the arsenal of cancer therapeutics [24,25] .…”

Section: Discussionmentioning

confidence: 99%

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

Xu¹,

Wang²,

Zou³

2008

WJG

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AIM:To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro , and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS:The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazol tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS:TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (MzChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. C O N C L U S I O N :T S A c a n i n h i b i t t h e g r o w t h o f cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

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Enhanced Histone Acetylation and Transcription: A Dynamic Perspective

Cited by 421 publications

References 76 publications

The Role of Histone Acetylation in Regulating Early Gene Expression Patterns during Early Embryonic Stem Cell Differentiation

The Role of Histone Acetylation in Regulating Early Gene Expression Patterns during Early Embryonic Stem Cell Differentiation

Histone Acetylation Facilitates Rapid and Robust Memory CD8 T Cell Response through Differential Expression of Effector Molecules (Eomesodermin and Its Targets: Perforin and Granzyme B)

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

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