Histone acetyltransferase complexes

Grant, Patrick A.; Berger, Shelley L.

doi:10.1006/scdb.1999.0298

Cited by 108 publications

(84 citation statements)

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“…Transcriptional competence is governed by histone acetylation status, which is determined by two families of enzymes, histone acetyltransferases (HATs) (Grant and Berger, 1999) and histone deacetylases (HDACs) (Cress and Seto, 2000). HATs promote acetylation of lysines on histone proteins and thereby destabilize the static bonds between DNA phosphates and histones, resulting in an open DNA conformation for gene transcription.…”

mentioning

confidence: 99%

Chemoresistance to Depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-Ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] Is Mediated by Reversible MDR1 Induction in Human Cancer Cell Lines

Xiao

Huang

Dai

et al. 2005

J Pharmacol Exp Ther

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Histone acetylation status, an epigenetic determinant of gene transcription, is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The potent HDAC inhibitor -oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is a substrate for multidrug resistance protein (MDR1) and multidrug resistance-associated protein 1 (MRP1), both of which mediate FK228 resistance. To determine the mechanisms underlying acquired FK228 resistance, we developed four FK228-resistant cell lines from HCT-15, IGROV1, MCF7, and K562 cells by stepwise increases in FK228 exposure. Parent and resistant cells were characterized using a 70-oligomer cDNA microarray, real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and cytotoxicity assays. At both mRNA and protein levels, MDR1, but not MRP1 or other potential resistance genes, was strongly up-regulated in all resistant cell lines. HAT or HDAC activities were unaffected in resistant cells, consistent with a lack of cross-resistance to HDAC inhibitors that are not MDR1 substrates. FK228 was found to reversibly induce MDR1 expression by HDAC inhibition and subsequent histone hyperacetylation at the MDR1 promoter, as shown by real-time RT-PCR, Western blot, and chromatin immunoprecipitation. This study reveals a significant role of histone acetylation in MDR1 transcription, which seems to mediate FK228 resistance.

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mentioning

confidence: 99%

Chemoresistance to Depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-Ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] Is Mediated by Reversible MDR1 Induction in Human Cancer Cell Lines

Xiao

Huang

Dai

et al. 2005

J Pharmacol Exp Ther

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“…The PCAF-related transcriptional co-activator/acetyltransferase GCN5 is a component of the SAGA complex in yeast (y) (reviewed in Ref. 45). The human homologues of the SAGA complex consist of three distinct complexes, i.e.…”

mentioning

confidence: 99%

E2F Transcriptional Activation Requires TRRAP and GCN5 Cofactors

Lang

McMahon

Cole

et al. 2001

Journal of Biological Chemistry

115

101

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The E2F family of transcription factors regulates the temporal transcription of genes involved in cell cycle progression and DNA synthesis. E2F transactivation is antagonized by retinoblastoma protein (pRb), which recruits chromatin-remodeling proteins such as histone deacetylases and SWI⅐SNF complexes to the promoter to repress transcription. We hypothesized that E2F proteins must reverse the pRb-imposed chromatin structure to stimulate transcription. If this is true, E2F proteins should recruit proteins capable of histone acetylation. Here we map the E2F-4 transactivation domain and show that E2F-1 and E2F-4 transactivation domains bind the acetyltransferase GCN5 and cofactor TRRAP in vivo. TRRAP and GCN5 co-expression stimulated E2F-mediated transactivation, and c-Myc repressed E2F transactivation dependent on an intact TRRAP/GCN5 binding motif. The transactivation domain of E2F-4 recruited proteins with significant histone acetyltransferase activity in vivo, and this activity required catalytically active GCN5. E2F-4 proteins with subtle mutations in the transactivation domain exhibited a positive correlation among transcriptional activation and GCN5 and TRRAP binding capacity and associated acetyltransferase activity. We conclude that E2F stimulates transcription by recruiting acetyltransferase activity and the essential cofactors GCN5 and TRRAP. These results provide a mechanism for E2F transcription factors to overcome pRb-mediated dominant repression of transcription.The cell cycle is regulated in part by the temporal expression of specific genes. A transcription factor can control the timely induction of S phase-specific genes by either activating gene expression shortly before and during S phase or repressing expression during the remainder of the cell cycle. The E2F family of transcription factors is thought to contribute to cell cycle regulation through both mechanisms. E2F is likely to be a critical factor in cell growth regulation in vivo since most if not all human cancers contain a disruption in the E2F regulatory pathway (1).Consistent with this, enforced expression of E2F proteins drives quiescent cells into S phase and transforms cells in conjunction with activated Ras (2-6). Furthermore, E2F binding sites are found in the promoters of numerous genes whose expression is necessary for the initiation of S phase and DNA replication (7-9).DNA binding activity of the E2F transcription factor family is composed of two subunits, E2F and DP, which form heterodimeric complexes with a high affinity for the DNA sequence 5Ј-TTTCGCG-3Ј (7-9). Currently, the mammalian E2F family consists of six E2F and two DP genes. The DNA binding, heterodimerization, and marked box domains are highly conserved among all E2F family members. E2F-1, -2, and -3 have an extended N-terminal region containing a nuclear localization signal and binding sites for cyclin A, the transcription factor Sp1, and the E3 ubiquitin ligase complex SCF⅐SKP2 (10 -17). E2F-4, -5, and -6 lack these sequences. E2Fs 1-5 have an acidic transactivat...

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“…25,29 The acetylation and deacetylation of histones are dynamic processes that depend on the balance between histone acetyltransferases and HDACs. 28,30 Histone acetyltransferases can transfer the acetyl moiety from acetyl coenzyme A onto the lysine residues of histone proteins, whereas HDACs usually repress transcription. 30 Unlike histone acetylation, histone methylation possesses a dual role in gene expression and may either activate or repress gene expression, which mainly depends on the sites of methylation.…”

Section: Epigeneticsmentioning

confidence: 99%

“…28,30 Histone acetyltransferases can transfer the acetyl moiety from acetyl coenzyme A onto the lysine residues of histone proteins, whereas HDACs usually repress transcription. 30 Unlike histone acetylation, histone methylation possesses a dual role in gene expression and may either activate or repress gene expression, which mainly depends on the sites of methylation. 31 For example, H3 K9 and K27 methylations are associated with transcriptional silencing, whereas methylations of K4, K36 and K79 of H3 have been associated with gene activity.…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetic regulation of pulmonary arterial hypertension

Cheng

2011

Hypertens Res

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Pulmonary arterial hypertension (PAH) is diagnosed as a sustained elevation of pulmonary arterial pressure to more than 25 mm Hg at rest or to more than 30 mm Hg with exercise. PAH is an intrinsic disease of the pulmonary vascular smooth muscle and endothelial cells in association with plexiform lesions, medial thickening, concentric laminar intimal fibrosis and thrombotic lesions. Pulmonary vascular remodeling is the characteristic pathological change of PAH. The pathogenesis of PAH has been studied at the level of smooth muscle and endothelial cells. Existing research does not adequately explain susceptibility to the disease, and recent evidence reveals that epigenetic alterations may be involved in PAH. Epigenetics refers to all heritable changes in phenotype or in gene expression states, including chromatin remodeling, DNA methylation, histone modification and RNA interference, which are not involved in the DNA sequence itself. This review will focus on recent advances in epigenetics related to PAH, including epigenetic changes of superoxide dismutase, endothelial nitric oxide synthase and the bone morphogenetic protein signaling pathway. This will provide new insight for improved treatment and prevention of PAH. Future work aimed at specific epigenetic treatments may prove to be an effective therapy for patients with PAH.

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Histone acetyltransferase complexes

Cited by 108 publications

References 0 publications

Chemoresistance to Depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-Ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] Is Mediated by Reversible MDR1 Induction in Human Cancer Cell Lines

Chemoresistance to Depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-Ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] Is Mediated by Reversible MDR1 Induction in Human Cancer Cell Lines

E2F Transcriptional Activation Requires TRRAP and GCN5 Cofactors

Epigenetic regulation of pulmonary arterial hypertension

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