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: 4.6). 03/2011; 286(16):13925-36. DOI: 10.1074/jbc.M111.223198
Source: PubMed

ABSTRACT 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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    ABSTRACT: Trefoil Factor 1 belongs to a group of small secreted proteins (the Trefoil Factor Family proteins), that are localized within the mucous granules and are expressed and secreted by epithelial cells that line mucous membranes. Trefoil Factors are mainly expressed in the gastrointestinal tract, where they normally contribute to maintain the integrity of the mucosa. We recently demonstrated a selective binding ability of Trefoil Factor 1 for copper ions, through its carboxy-terminal tail, and we also observed that copper levels influence the equilibrium between the monomeric and homodimeric forms of Trefoil Factor 1, thus modulating its biological activity. Here we report that transcriptional regulation of Trefoil Factor 1 is also affected by copper levels, through the modulated binding of the copper-sensing transcription factor Sp1 onto the responsive elements present in the regulatory region of the gene. In addition we demonstrate that copper overload causes an accumulation of the trefoil protein in the Trans-Golgi Network and that Trefoil Factor 1 levels can influence copper excretion and copper related toxicity. These findings suggest that the protein might play a role in the overall complex mechanisms of copper homeostasis in the gastrointestinal tissues. Copyright © 2014. Published by Elsevier Ltd.
    The International Journal of Biochemistry & Cell Biology 12/2014; 59. DOI:10.1016/j.biocel.2014.11.014 · 4.24 Impact Factor
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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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    • "Upon PR-Set7 knockdown, wnt3a-dependent activation of wnt response genes was abolished. This regulation was shown to be physiologically relevant, since PR-Set7 participates in the wnt developmental pathway in zebrafish (Z Li et al. 2011). These results are slightly complicated by the fact that PR-Set7 was found to both stimulate and repress the wnt3a response genes potentially by cooperating with Lef3, a known transcriptional activator and repressor. "
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    ABSTRACT: Histone post-translational modifications impact many aspects of chromatin and nuclear function. Histone H4 Lys 20 methylation (H4K20me) has been implicated in regulating diverse processes ranging from the DNA damage response, mitotic condensation, and DNA replication to gene regulation. PR-Set7/Set8/KMT5a is the sole enzyme that catalyzes monomethylation of H4K20 (H4K20me1). It is required for maintenance of all levels of H4K20me, and, importantly, loss of PR-Set7 is catastrophic for the earliest stages of mouse embryonic development. These findings have placed PR-Set7, H4K20me, and proteins that recognize this modification as central nodes of many important pathways. In this review, we discuss the mechanisms required for regulation of PR-Set7 and H4K20me1 levels and attempt to unravel the many functions attributed to these proteins.
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