The Histone Modifications Governing TFF1 Transcription Mediated by Estrogen Receptor

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2011; 286(16):13925-36. DOI: 10.1074/jbc.M111.223198
Source: PubMed


Transcription regulation by histone modifications is a major contributing factor to the structural and functional diversity in biology. These modifications are encrypted as histone codes or histone languages and function to establish and maintain heritable epigenetic codes that define the identity and the fate of the cell. Despite recent advances revealing numerous histone modifications associated with transcription regulation, how such modifications dictate the process of transcription is not fully understood. Here we describe spatial and temporal analyses of the histone modifications that are introduced during estrogen receptor α (ERα)-activated transcription. We demonstrated that aborting RNA polymerase II caused a disruption of the histone modifications that are associated with transcription elongation but had a minimal effect on modifications deposited during transcription initiation. We also found that the histone H3S10 phosphorylation mark is catalyzed by mitogen- and stress-activated protein kinase 1 (MSK1) and is recognized by a 14-3-3ζ/14-3-3ε heterodimer through its interaction with H3K4 trimethyltransferase SMYD3 and the p52 subunit of TFIIH. We showed that H3S10 phosphorylation is a prerequisite for H3K4 trimethylation. In addition, we demonstrated that SET8/PR-Set7/KMT5A is required for ERα-regulated transcription and its catalyzed H4K20 monomethylation is implicated in both transcription initiation and elongation. Our experiments provide a relatively comprehensive analysis of histone modifications associated with ERα-regulated transcription and define the biological meaning of several key components of the histone code that governs ERα-regulated transcription.

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    • "Regulation of TFF1 expression has been extensively analysed, and the reported evidence of DNA methylation (Métivier et al., 2008) and histone modifications (Li et al., 2011) shed further light on the role of the epigenetic control. Moreover a number of transcription factors were described to bind its promoter and control its expression: the already mentioned Estrogen Receptor along with Sp proteins (Sun et al., 2005), as well as TNF-␣ activated NF-␬B (Koike et al., 2007) and the AP-1 complex (Baron et al., 2007). "
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    • "Epigenetic regulation of the AHR pathway, including the Ahr gene itself, is likely to play an important role in the control of the expression of its target genes, and thus, in its biological functions and its mechanistic role in xenobiotic metabolism and developmental toxicity. Of the three protein kinases detected, MSK1/2 has been shown to induce the expression of early stress response genes, such as c-fos and c-jun, by phosphorylation of H3S10 after mitogen stimulation (Soloaga et al., 2003), and to regulate TFF1 transcription by phosphorylating H3S10 in the TFF1 promoter in an ER␣-dependent manner (Li et al., 2011b). In addition, MSK1/2 has been associated with the activation of the AHR pathway for quite some time. "
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    • "Therefore, PR-Set7, but not Riz1, is necessary for repression of specific genes, most likely by monomethylating H4K20. PR-Set7 and Riz1 were also reported to function in gene activation, including the induction of estrogen-responsive genes, suggesting a possible role for the H4K20me1-H3K9me1 trans-tail ‘histone code’ in these pathways (27,28). Although PR-Set7 and Riz1 primarily function in gene repression, further investigation is required to examine their possible function in gene activation. "
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