HBO1 HAT Complexes Target Chromatin throughout Gene Coding Regions via Multiple PHD Finger Interactions with Histone H3 Tail

Saksouk, Nehmé; Avvakumov, Nikita; Champagne, Karen S.; Hung, Tiffany; Doyon, Yannick; Cayrou, Christelle; Paquet, Éric R.; Ullah, Mukta; Landry, Anne-Julie; Côté, Valérie; Yang, Xiang-Jiao; Gozani, Or; Kutateladze, Tatiana G.; Côté, Jacques

doi:10.1016/j.molcel.2009.01.007

Cited by 160 publications

(215 citation statements)

References 20 publications

(35 reference statements)

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“…However, increased promoter occupancy by RelA in Ing4 −/− cells does not result in increased activation of all cytokines following LPS treatment, as Ing4 is required for proper H4 acetylation of select NF-κB responsive promoters, such as TNF-α and KC. This finding is in agreement with a recently published report suggesting that ING4-containing HBO1 complexes are responsible for acetylation of H4 and possibly transcription elongation (18).…”

Section: Discussionsupporting

confidence: 94%

“…Thus, ING4 was proposed to inhibit cell survival and angiogenesis by complexing with and inhibiting RelA (7). More recently, transfection and knock-down experiments performed in glioma cell lines have indicated that ING4 may regulate NF-κB activity by binding simultaneously with RelA to NF-κB promoters and altering the levels of promoter histone acetylation (18). However, the precise role of ING4 regulation of NF-κB activity in cancer is unclear, and definitive proof that ING4 regulates tumorigenesis is lacking.…”

mentioning

confidence: 99%

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Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Coles¹,

Gannon²,

Cerny³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Ing4 is a member of the inhibitor of growth (ING) family of chromatin-modifying proteins. Biochemical experiments indicate that Ing4 is a subunit of the HB01-JADE-hEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation in eukaryotes, and transfection studies suggest that Ing4 may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression. However, in vivo evidence for a physiological role for Ing4 in cell-growth regulation is lacking. We have generated Ing4-deficient mice to explore the role of Ing4 in development, tumorigenesis, and in NF-κB signaling. Ing4-null mice develop normally and are viable. Although mice deficient for Ing4 fail to form spontaneous tumors, they are hypersensitive to LPS treatment and display elevated cytokine responses. Macrophages isolated from Ing4-null mice have increased levels of nuclear p65/RelA protein, resulting in increased RelA binding to NF-κB target promoters and up-regulation of cytokine gene expression. However, increased promoter occupancy by RelA in LPS-stimulated, Ing4-null cells does not always correlate with increased NF-κB target-gene expression, as RelA activation of a subset of cytokine promoters also requires Ing4 for proper histone H4 acetylation. Furthermore, activation of the IκBα promoter by RelA is also Ing4-dependent, and LPS-stimulated, Ing4-null cells have reduced levels of IκBα promoter H4 acetylation and IκB gene expression. Thus, Ing4 negatively regulates the cytokine-mediated inflammatory response in mice by facilitating NF-κB activation of IκB promoters, thereby suppressing nuclear RelA levels and the activation of select NF-κB target cytokines.

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Section: Discussionsupporting

confidence: 94%

mentioning

confidence: 99%

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Coles¹,

Gannon²,

Cerny³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In support of this mechanism WDR5 knockdown, which depletes H3K4 methylation (48), attenuates the TSA-induced increase in H3K9ac levels at promoters (18). Other KATs are known to be recruited to H3K4me3 to induce histone acetylation; yeast Yng1 and Yng2, which recognize H3K4me3 via their plant homeo domain (PHD) fingers (49, 50), form part of the NuA3 and NuA4 KAT complexes, respectively (51,52), and mammalian ING4 links HBO1 acetyltransferase activity to H3 lysine-4 trimethylated nucleosomes (53,54).…”

Section: Cotargeting Of H3k4 Trimethylation and Dynamic Acetylation Tmentioning

confidence: 99%

Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP

Crump

Hazzalin

Bowers

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

111

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Histone modifications are reported to show different behaviors, associations, and functions in different genomic niches and organisms. We show here that rapid, continuous turnover of acetylation specifically targeted to all K4-trimethylated H3 tails (H3K4me3), but not to bulk histone H3 or H3 carrying other methylated lysines, is a common uniform characteristic of chromatin biology in higher eukaryotes, being precisely conserved in human, mouse, and Drosophila. Furthermore, dynamic acetylation targeted to H3K4me3 is mediated by the same lysine acetyltransferase, p300/cAMP response element binding (CREB)-binding protein (CBP), in both mouse and fly cells. RNA interference or chemical inhibition of p300/CBP using a newly discovered small molecule inhibitor, C646, blocks dynamic acetylation of H3K4me3 globally in mouse and fly cells, and locally across the promoter and start-site of inducible genes in the mouse, thereby disrupting RNA polymerase II association and the activation of these genes. Thus, rapid dynamic acetylation of all H3K4me3 mediated by p300/CBP is a general, evolutionarily conserved phenomenon playing an essential role in the induction of immediate-early (IE) genes. These studies indicate a more global function of p300/CBP in mediating rapid turnover of acetylation of all H3K4me3 across the nuclei of higher eukaryotes, rather than a tight promoter-restricted function targeted by complex formation with specific transcription factors.histone acetylation turnover | Trichostatin A | p300/CBP inhibitor

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“…The conserved domains of ING4 are essential in the modulation of its function. The PHD finger serves as an important effector domain for its binding to the H3K4me3 and HAT complex [13]. ING4 associates with p53 via its NLS region, leading to enhanced acetylation of p53 on Lys-382 and transcriptional activity of p53 [24,27].…”

Section: Discussionmentioning

confidence: 99%

“…ING4 has been shown to be involved in chromatin remodeling through recognition of trimethylated-K4 in the histone-3 tail (H3K4me3) via its conserved PHD domain [13]. We next investigated whether nucleic acid, including RNA and DNA, affected the binding of ING4 and AUF1 using co-IP assays in K562 cells.…”

Section: Ing4 Associates With Myc Mrnamentioning

confidence: 99%

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

et al. 2013

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a b s t r a c tThe ING4 tumor suppressor plays a significant role in various cancer-related cellular processes. AUF1 affects the stability and/or translation of multiple mRNAs via binding to an AU-rich element in the 3 0 -untranslated regions. In this study, we identify AUF1 as a novel and direct binding partner of ING4. mRNP immunoprecipitation assays indicated that ING4, AUF1 and MYC mRNA present in the same mRNP complex. ING4 suppressed MYC protein expression without altering MYC mRNA levels, and abolished the cell proliferation induced by AUF1 in K562 cells. These results suggest that ING4 may regulate MYC translation by its association with AUF1. Structured summary of protein interactions:ING4binds to AUF1 p40 by pull down (View interaction) ING4physically interacts with AUF1 by anti tag coimmunoprecipitation (View Interaction: 1, 2) ING4binds to AUF1 p37 by pull down (View Interaction: 1, 2) ING4 binds to AUF1 p42 by pull down (View interaction) ING4binds to AUF1 p45 by pull down (View interaction) ING4physically interacts with AUF1 by anti bait coimmunoprecipitation (View Interaction: 1,2,3,4,5,6) ING4binds to AUF1 by pull down (View interaction)

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HBO1 HAT Complexes Target Chromatin throughout Gene Coding Regions via Multiple PHD Finger Interactions with Histone H3 Tail

Cited by 160 publications

References 20 publications

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

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