Miotto B, Sagnier T, Berenger H, Bohmann D, Pradel J, Graba Y.. Chameau HAT and DRpd3 HDAC function as antagonistic cofactors of JNK/AP-1-dependent transcription during Drosophila metamorphosis. Genes Dev 20: 101-112

University of Rochester, Rochester, New York, United States
Genes & Development (Impact Factor: 10.8). 02/2006; 20(1):101-12. DOI: 10.1101/gad.359506
Source: PubMed


Gene regulation by AP-1 transcription factors in response to Jun N-terminal kinase (JNK) signaling controls essential cellular processes during development and in pathological situations. Here, we report genetic and molecular evidence that the histone acetyltransferase (HAT) Chameau and the histone deacetylase DRpd3 act as antagonistic cofactors of DJun and DFos to modulate JNK-dependent transcription during thorax metamorphosis and JNK-induced apoptosis in Drosophila. We demonstrate in cultured cells that DFos phosphorylation mediated by JNK signaling plays a central role in coordinating the dynamics of Chameau and DRpd3 recruitment and function at AP-1-responsive promoters. Activating the pathway stimulates the HAT function of Chameau, promoting histone H4 acetylation and target gene transcription. Conversely, in response to JNK signaling inactivation, DRpd3 is recruited and suppresses histone acetylation and transcription. This study establishes a direct link among JNK signaling, DFos phosphorylation, chromatin modification, and AP-1-dependent transcription and its importance in a developing organism.

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Available from: Benoit Miotto, May 21, 2014
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    • "Error bars represent mean ±SD, n = 4. p-value of two-tailed Student's t-test is indicated.Chameau subfamily of the MYST family histone acetyltransferases has been mainly considered to function in an epigenetic mechanism of transcriptional repression since haploinsufficiency of Chameau leads to defects of position effect variegation[14]. Recently, it was also shown that Chameau cooperates with JNK signaling to promote transcriptional activation[15]and Hbo1, the human homologue of Chameau, is required for H3K14 acetylation and normal transcriptional activity during embryonic development[17]. These contradictory observations can be explained by either multiple targets or a co-regulator of Chameau. "
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    DESCRIPTION: EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.
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    • "Of note, in the present study, Rh2 inhibited pAP-1-luc luciferase activity, which suggested that Rh2 remodels AP-1 transcription factors. Miotto et al (29) reported that the interactions among AP-1 and partner molecules modified and remodeled chromatin by recruiting DRpd3/HDAC1 to reverse histone acetylation. Other reports on the stimulation of Fos or Jun activities by CREB-binding protein suggested that the recruitment of HAT coactivator complexes at target promoters mediates nucleosome acetylation and stimulates transcription (29). "
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    ABSTRACT: In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest, which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown to inhibit pancreatic tumor migratory ability. In the present study, Transwell chambers were used in order to investigate whether ginsenoside Rh2 inhibits the migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze activator protein 1 (AP‑1) transcription factor expression following Rh2 treatment, ten plasmids encoding Renilla luciferase coupled to the transcription factors were transiently transfected into the HepG2 cells and luciferase was detected by the Luciferase Reporter Assay system reagent. The results indicated that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression levels of AP‑1 transcription factors were increased in HepG2 cells following induction by phorbol 12‑myristate 13‑acetate, but ginsenoside Rh2 suppressed this induced AP‑1 expression. AP‑1 transcription factors recruit histone deacetylase (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were also analyzed, and these were found to be increased in the Rh2 treatment group. Matrix metalloproteinase 3 (MMP3), a gene downstream of AP‑1, was then investigated, and the treatment group expressed reduced levels of MMP3 gene and protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory ability of HepG2 may be presumed to occur by the recruitment of HDAC and the resulting inhibition of AP‑1 transcription factors, in order to reduce the expression levels of MMP3 gene and protein.
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    • "Null mutations of the gcn5, Ada2a or Ada2b genes cause lethality at the end of the third larval instar or in early pupae [11], [24], therefore we analyzed the level of acetyl-H3K23 in late L3 larvae in which GCN5 activity supposed to reach critically low levels. We tested samples from homozygous gcn5E333St, Ada2a189 and Ada2b842 mutants next to homozygous chm14, mof2 (two H4K16 specific HATs [25], [26]) and w1118 (wild-type) controls by western analysis and found that loss of neither of these factors led to decreased H3K23 acetylation (Fig. 4A). "
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    ABSTRACT: Posttranslational modification of histones regulates transcription but the exact role that acetylation of specific lysine residues plays in biological processes in vivo is still not clearly understood. To assess the contribution of different histone modifications to transcriptional activation in vivo, we determined the acetylation patterns on the ecdysone induced Eip74EF and Eip75B genes in Drosophila melanogaster larvae by chromatin immunoprecipitation. We found that acetylation of histone H3 lysine 23 is localized to promoters and correlates with endogenous ecdysone induced gene activation. In contrast, acetylation of lysines 8, 12 and 16 of histone H4 and lysine 9 of histone H3 showed minor differences in their distribution on the regulatory and transcribed regions tested, and had limited or no correlation with ecdysone induced transcriptional activity. We found that dCBP, which is encoded by the nejire gene, acetylates H3 lysine 23 in vivo, and silencing of nejire leads to reduced expression of the Eip74EF and Eip75B genes. Our results suggest that acetylation of specific lysine residues of histones contribute specifically to the dynamic regulation of transcription. Furthermore, along with previous studies identify CBP dependent H3 lysine 23 acetylation as an evolutionarily conserved chromatin modification involved in steroid induced gene activation.
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