The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output

Stijf-Bultsma, Yvette; Sommer, Lilly; Tauber, Maria; Baalbaki, Mai; Giardoglou, Panagiota; Jones, David R.; Gelato, Kathy A.; Pelt, Jason van; Shah, Zahid H.; Rahnamoun, Homa; Toma, Clara; Anderson, Karen E.; Hawkins, Phillip T.; Lauberth, Shannon; Haramis, Anna-Pavlina G.; Hart, Daniel; Fischle, Wolfgang; Divecha, Nullin

doi:10.1016/j.molcel.2015.03.009

Cited by 60 publications

(72 citation statements)

References 60 publications

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“…C2C12 cells depleted of endogenous TAF3 were reconstituted with either wild type or mutant KK-TAF3 and then PIP4K2B was knocked down. The data clearly demonstrate that the expression of a subset of PIP4K2B-regulated myogenic genes requires the intact phosphoinositide interacting PHD finger of TAF3 [46]. Similar results were observed for PtdIns5P-mediated regulation of gene expression by the PHD finger containing protein ING2 (inhibitor of growth protein 2) under conditions of stress [55].…”

Section: Nuclear Turtles and Taf3 Promote Muscle Differentiationsupporting

confidence: 77%

“…In a recent study 17 out of 32 different PHD fingers tested interacted with phosphoinositides [46]. Phosphoinositide interaction was not associated with any other function of PHD fingers such as H3K4me3 interaction and was observed with PHD fingers derived from proteins that function as writers, erasers and readers [46]. These data suggest that nuclear Phosphoinositides are likely to play a significant role in regulating chromatin conformation and transcriptional output.…”

Section: Knowing Your Turtle's Friends Illuminates the Pathwaymentioning

confidence: 93%

“…Critically PHD fingers also interact with phosphoinositides. In a recent study 17 out of 32 different PHD fingers tested interacted with phosphoinositides [46]. Phosphoinositide interaction was not associated with any other function of PHD fingers such as H3K4me3 interaction and was observed with PHD fingers derived from proteins that function as writers, erasers and readers [46].…”

Section: Knowing Your Turtle's Friends Illuminates the Pathwaymentioning

confidence: 97%

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Phosphoinositides in the nucleus and myogenic differentiation: how a nuclear turtle with a PHD builds muscle

Divecha

2016

Biochemical Society Transactions

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Phosphoinositides are a family of phospholipid messenger molecules that control various aspects of cell biology in part by interacting with and regulating downstream protein partners. Importantly, phosphoinositides are present in the nucleus. They form part of the nuclear envelope and are present within the nucleus in nuclear speckles, intra nuclear chromatin domains, the nuclear matrix and in chromatin. What their exact role is within these compartments is not completely clear, but the identification of nuclear specific proteins that contain phosphoinositide interaction domains suggest that they are important regulators of DNA topology, chromatin conformation and RNA maturation and export. The plant homeo domain (PHD) finger is a phosphoinositide binding motif that is largely present in nuclear proteins that regulate chromatin conformation. In the present study I outline how changes in the levels of the nuclear phosphoinositide PtdIns5P impact on muscle cell differentiation through the PHD finger of TAF3 (TAF, TATA box binding protein (TBP)-associated factor), which is a core component of a number of different basal transcription complexes.

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Section: Nuclear Turtles and Taf3 Promote Muscle Differentiationsupporting

confidence: 77%

Section: Knowing Your Turtle's Friends Illuminates the Pathwaymentioning

confidence: 93%

Section: Knowing Your Turtle's Friends Illuminates the Pathwaymentioning

confidence: 97%

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Phosphoinositides in the nucleus and myogenic differentiation: how a nuclear turtle with a PHD builds muscle

Divecha

2016

Biochemical Society Transactions

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“…Dissection of the C-terminal domains of Yng2 showed that it contains a PHD motif followed by a frequently associated polybasic region (PBR). Other PHD/PBRcontaining proteins, such as ING2, Pf1, and TAF3, have been shown to bind phosphoinositides (phosphatidylinositol biphosphate or phosphatidylinositol triphosphate), and this binding is important for phospholipid-dependent nuclear signaling and gene expression, arguably through cross talk with recognition of H3K4 by the PHD (58)(59)(60)(61)(62). In order to evaluate the function and the biochemical properties of these domains, we generated mutants with mutations in these two regions (Fig.…”

Section: Resultsmentioning

confidence: 99%

Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

Steunou

Cramet

Rossetto

et al. 2016

Molecular and Cellular Biology

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e Recognition of histone marks by reader modules is thought to be at the heart of epigenetic mechanisms. These protein domains are considered to function by targeting regulators to chromosomal loci carrying specific histone modifications. This is important for proper gene regulation as well as propagation of epigenetic information. The NuA4 acetyltransferase complex contains two of these reader modules, an H3K4me3-specific plant homeodomain (PHD) within the Yng2 subunit and an H3K36me2/3-specific chromodomain in the Eaf3 subunit. While each domain showed a close functional interaction with the respective histone mark that it recognizes, at the biochemical level, genetic level (as assessed with epistatic miniarray profile screens), and phenotypic level, cells with the combined loss of both readers showed greatly enhanced phenotypes. Chromatin immunoprecipitation coupled with next-generation sequencing experiments demonstrated that the Yng2 PHD specifically directs H4 acetylation near the transcription start site of highly expressed genes, while Eaf3 is important downstream on the body of the genes. Strikingly, the recruitment of the NuA4 complex to these loci was not significantly affected. Furthermore, RNA polymerase II occupancy was decreased only under conditions where both PHD and chromodomains were lost, generally in the second half of the gene coding regions. Altogether, these results argue that methylated histone reader modules in NuA4 are not responsible for its recruitment to the promoter or coding regions but, rather, are required to orient its acetyltransferase catalytic site to the methylated histone 3-bearing nucleosomes in the surrounding chromatin, cooperating to allow proper transition from transcription initiation to elongation. Chromatin is a dynamic nucleoprotein structure that compacts the long DNA molecule into the small nuclear space, simultaneously creating a mechanism to regulate DNA access to machineries implicated in essential nuclear processes, namely, transcription, DNA replication, DNA repair, and meiotic recombination. Modulation of the chromatin structure is highly regulated by four broad classes of nuclear factors: chromatin remodelers, histone chaperones, histone variants, and histone modifiers. These players essentially target nucleosomes, basic units of chromatin consisting of 146 bp of DNA wrapped around an octamer of histone proteins. Histone modifiers catalyze posttranslational modifications (PTM), including acetylation, phosphorylation, and methylation, that can directly affect DNA-histone contacts (e.g., acetylation) and/or create a binding platform for PTM readers (1, 2). These readers correspond to proteins/complexes containing distinct domains/modules that can bind specific modified histone residues. Such motifs include bromodomains that recognize acetylated residues; chromodomains (CHD); PWWP, Tudor, and MBT domains for methylated residues; BRCT, BIR, and 14-3-3 domains for phosphorylated histones; and plant homeodomain (PHD) fingers that can bind different modification...

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“…One example of the latter scenario is the STAR-PAP poly-A RNA polymerase that uses PtdIns-4,5-P 2 as essential cofactor (23,24). Other examples include direct modification of a phosphoinositide bound to the nuclear receptor by inositide multikinase kinase (25,26) and control of the basal transcription machinery by nuclear phosphoinositides (27).…”

Section: Implications For Nuclear Pl Signalingmentioning

confidence: 99%

Quantitative profiling of the endonuclear glycerophospholipidome of murine embryonic fibroblasts

Tribble

Ivanova

Grabon

et al. 2016

Journal of Lipid Research

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The mammalian nuclear matrix is now recognized as a site of lipid biosynthesis and signaling in both normal and pathological states (reviewed in 1-8). Radioisotope and stable isotope tracer studies consistently identify glycerophospholipids (GPLs), and the enzymatic activities that metabolize them, within purified nuclear fractions purportedly devoid of nuclear envelope and other cellular membrane contaminants (9-15). These findings suggest the existence of an independently-regulated GPL pool within the nuclear matrix, one distinct from the nuclear envelope and from bulk cellular membranes. In support of this interpretation, nuclear isoforms of a number of GPL metabolic enzymes have been described (10,11,(16)(17)(18)(19)(20)(21)(22). The STAR-PAP RNA poly-A polymerase, the direct modification of a phosphoinositide headgroup presented to an inositide kinase by a nuclear receptor, and nuclear phosphoinositide control of the basal transcription machinery all provide compelling examples of GPL-regulated activities that discharge their functions within the nuclear matrix (23-27). At issue, however, is the scale of nuclear GPL metabolism and nuclear GPL load.This difficult question can now be addressed using quantitative mass spectrometric methods. The single major study on this topic estimates that phosphatidylcholine (PtdCho) alone occupies 10-16% of the nuclear matrix of IRB-32 cells by volume (14). This is a startling conclusion Abstract A reliable method for purifying envelope-stripped nuclei from immortalized murine embryonic fibroblasts (iMEFs) was established. Quantitative profiling of the glycerophospholipids (GPLs) in envelope-free iMEF nuclei yields several conclusions. First, we find the endonuclear glycerophospholipidome differs from that of bulk membranes, and phosphatidylcholine (PtdCho) and phosphatidylethanolamine species are the most abundant endonuclear GPLs by mass. By contrast, phosphatidylinositol (PtdIns) represents a minor species. We also find only a slight enrichment of saturated versus unsaturated GPL species in iMEF endonuclear fractions. Moreover, much lower values for GPL mass were measured in the iMEF nuclear matrix than those reported for envelope-stripped IMF-32 nuclei. The collective results indicate that the nuclear matrix in these cells is a GPL-poor environment where GPL occupies only approximately 0.1% of the total nuclear matrix volume. This value suggests GPL accommodation in this compartment can be satisfied by binding to resident proteins. Finally, we find no significant role for the PtdIns/PtdChotransfer protein, PITP, in shuttling PtdIns into the iMEF nuclear

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The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output

Cited by 60 publications

References 60 publications

Phosphoinositides in the nucleus and myogenic differentiation: how a nuclear turtle with a PHD builds muscle

Phosphoinositides in the nucleus and myogenic differentiation: how a nuclear turtle with a PHD builds muscle

Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

Quantitative profiling of the endonuclear glycerophospholipidome of murine embryonic fibroblasts

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