Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation

Brownell, James E.; Zhou, Jianxin; Ranalli, Tammi A.; Kobayashi, Ryûji; Edmondson, Diane G.; Roth, Sharon Y.; Allis, C. David

doi:10.1016/s0092-8674(00)81063-6

Cited by 1,464 publications

(1,000 citation statements)

References 58 publications

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“…HAT complexes from both GNAT and MYST families were shown to be recruited to activator-bound nucleosomes resulting in transcriptional activation (Brownell et al, 1996;Vignali et al, 2000;Utley et al, 2005). The recruitment of SAGA leads to acetylation of promoter-proximal H3, whereas recruitment of NuA4 results in a broader domain of H4 acetylation (>3 kbp) (Vignali et al, 2000).…”

Section: Transcriptionmentioning

confidence: 99%

Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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Chromatin modifications at core histones including acetylation, methylation, phosphorylation and ubiquitination play an important role in diverse biological processes. Acetylation of specific lysine residues within the N terminus tails of core histones is arguably the most studied histone modification; however, its precise roles in different cellular processes and how it is disrupted in human diseases remain poorly understood. In the last decade, a number of histone acetyltransferases (HATs) enzymes responsible for histone acetylation, has been identified and functional studies have begun to unravel their biological functions. The activity of many HATs is dependent on HAT complexes, the multiprotein assemblies that contain one HAT catalytic subunit, adapter proteins, several other molecules of unknown function and a large protein called TRansformation/tRanscription domain-Associated Protein (TRRAP). As a common component of many HAT complexes, TRRAP appears to be responsible for the recruitment of these complexes to chromatin during transcription, replication and DNA repair. Recent studies have shed new light on the role of TRRAP in HAT complexes as well as mechanisms by which it mediates diverse cellular processes. Thus, TRRAP appears to be responsible for a concerted and context-dependent recruitment of HATs and coordination of distinct chromatin-based processes, suggesting that its deregulation may contribute to diseases. In this review, we summarize recent developments in our understanding of the function of TRRAP and TRRAP-containing HAT complexes in normal cellular processes and speculate on the mechanism underlying abnormal events that may lead to human diseases such as cancer.

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Section: Transcriptionmentioning

confidence: 99%

Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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“…Recent studies have shown that HAT acts as the transcriptional coactivator (Bannister and Kouzarides, 1996;Brownell et al, 1996;Mizzen et al, 1996;Ogryzko et al, 1996;Yang et al, 1996b) whereas HDAC behaves as the corepressor Hassig et al, 1997;Kadosh and Struhl, 1997;Laherty et al, 1997;Nagy et al, 1997;Yang et al, 1996a). Therefore, it seems reasonable that HDAC inhibitors exhibit various biological activities by directly a ecting the transcription of some endogenous genes.…”

Section: E Ects Of Oxam¯atin On Endogenous Gene Expressionmentioning

confidence: 99%

Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase

et al. 1999

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Oxam¯atin [(2E) -5 -[3 -[(phenylsufonyl) amino] phenyl]-pent-2-en-4-ynohydroxamic acid] induces transcriptional activation of junD and morphological reversion in various NIH3T3-derived transformed cell lines. We found that oxam¯atin showed in vitro antiproliferative activity against various mouse and human tumor cell lines with drastic changes in the cell morphology and in vivo antitumor activity against B16 melanoma. Oxam¯atin caused an elongated cell shape with ®lamentous protrusions as well as arrest of the cell cycle at the G1 phase in HeLa cells. These phenotypic changes of HeLa cells were apparently similar to those by trichostatin A (TSA), a speci®c inhibitor of histone deacetylase (HDAC). The e ect of oxam¯atin on the transcriptional activity of the cytomegalovirus (CMV) promoter was examined and compared with known HDAC inhibitors, TSA, sodium n-butyrate, and FR901228. Oxam¯atin as well as all these inhibitors greatly enhanced the transcriptional activity of the CMV promoter in a dose-dependent manner. Oxam¯atin, like TSA, inhibited intracellular HDAC activity, as a result of which marked amounts of acetylated histone species accumulated. Finally, e ects on expression of several endogenous genes involved in cell morphology and cell cycle control in HeLa cells were analysed. Expression of gelsolin, cyclin E and Cdk inhibitors including p21 WAF1/Cip1 was highly augmented, while that of cyclin A and cyclin D1 was decreased by oxam¯atin. These results suggest that changes in the expression pattern of the genes regulating cell morphology and the cell cycle due to histone hyperacetylation are responsible for the antitumor activity, the morphological change and the cell cycle arrest induced by oxam¯atin.

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“…Overall, it is proposed that acetylation levels regulate gene transcription by controlling the accessibility of transcription factors to DNA (Grunstein, 1997). Indeed, HAT and HDAC activity has been identified within transcriptional coactivators and corepressors, respectively, providing strong evidence of the functional connection between histone acetylation and transcription (Brownell et al, 1996;Alland et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Modulation of cellular radiation responses by histone deacetylase inhibitors

Karagiannis

El‐Osta

2006

Oncogene

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Histone deacetylase (HDAC) inhibitors are emerging as a new class of targeted cancer chemotherapeutics. Several HDAC inhibitors are currently in clinical trials and promising anticancer effects at well-tolerated doses have been observed for both hematologic and solid cancers. HDAC inhibitors have been shown to induce cell-cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. However, it is known that these compounds induce varying responses in different cells and biological settings, and identifying their precise mechanisms of action is an area of great interest. Important findings are continually expanding our understanding of the cellular effects of HDAC inhibitors and recent studies will be briefly outlined in this review. In addition to their intrinsic anticancer properties, numerous studies have demonstrated that HDAC inhibitors can modulate cellular responses to other cytotoxic modalities including ionizing radiation, ultraviolet radiation and chemotherapeutic drugs. Hence, there is a growing interest in potential clinical use of HDAC inhibitors in combination with conventional cancer therapies. In this review, the interaction of HDAC inhibitors with other anticancer agents is discussed. The focus of the article is on the different mechanisms by which HDAC inhibitors enhance the sensitivity of cells to the effects of ionizing radiation.

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Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation

Cited by 1,464 publications

References 58 publications

Orchestration of chromatin-based processes: mind the TRRAP

Orchestration of chromatin-based processes: mind the TRRAP

Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase

Modulation of cellular radiation responses by histone deacetylase inhibitors

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