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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

ABSTRACT

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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    • "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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    • "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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