Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells

Daftari, Pratibha; Gavva, Narender R.; Shen, C-K James

doi:10.1038/sj.onc.1202916

Cited by 36 publications

(33 citation statements)

References 47 publications

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“…NF-E2 interacts not only with the LCR (Daftari et al 1999;Forsberg et al 2000;Sawado et al 2001), but also with the promoter region, even though no canonical NF- E2 binding sites are present in the promoter (Sawado et al 2001). Previously, we proposed two models for sequence-independent NF-E2 recruitment to the promoter: NF-E2 may be recruited to the promoter via interaction between the LCR and the promoter; alternatively, NF-E2 may reside in two independent protein complexes that bind to the LCR and the active promoters (Sawado et al 2001).…”

Section: Nf-e2 and Pol II Recruitment To The ␤-Globin Promoter Are Lcmentioning

confidence: 99%

The β-globinlocus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation

Sawado¹,

Halow²,

Bender³

et al. 2003

Genes Dev.

164

166

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To investigate the molecular basis of ␤-globin gene activation, we analyzed factor recruitment and histone modification at the adult ␤-globin gene in wild-type (WT)/locus control region knockout (⌬LCR) heterozygous mice and in murine erythroleukemia (MEL) cells. Although histone acetylation and methylation (Lys 4) are high before and after MEL differentiation, recruitment of the erythroid-specific activator NF-E2 to the promoter and preinitiation complex (PIC) assembly occur only after differentiation. We reported previously that targeted deletion of the LCR reduces ␤-globin gene expression to 1%-4% of WT without affecting promoter histone acetylation. Here, we report that NF-E2 is recruited equally efficiently to the adult ␤-globin promoters of the ⌬LCR and WT alleles. Moreover, the LCR deletion reduces PIC assembly only twofold, but has a dramatic effect on Ser 5 phosphorylation of RNA polymerase II and transcriptional elongation. Our results suggest at least three distinct stages in ␤-globin gene activation: (1) [Keywords: Allele-specific chromatin immunoprecipitation analysis; locus control region; ␤-globin locus; transcription elongation; NF-E2; CTD-phosphorylation] Supplemental material is available at http://www.genesdev.org. Received January 6, 2003; revised version accepted February 19, 2003. In higher eukaryotes, gene activation involves several events including chromatin opening, activator binding to regulatory regions, recruitment of basal transcription factors (TFIIA to TFIIJ) and RNA polymerase II (pol II) to the promoter [preinitiation complex (PIC) assembly], and transcription elongation. A general model has emerged in which activators function to stabilize or modulate transcription through interactions with histone acetyltransferases, as well as components of the basal transcription machinery, such as TATA binding protein (TBP), TBP-associated factors (TAFs), and TFIIB (for review, see Lemon and Tjian 2000). PIC assembly is followed by initiation and elongation, during which the Cterminal domain (CTD) of the RPB1 subunit of pol II is phosphorylated (for review, see Dahmus 1996). These steps in gene activation are often regulated by distal elements called enhancers (for review, see Blackwood and Kadonaga 1998;Martin 2001). Enhancers increase either the rate of transcription, the number of the templates engaged in transcription, or both. Studies using transgenes or in vitro templates have linked enhancer activities to various events such as PIC assembly (Kim et al. 1998;Yie et al. 1999), histone acetylation at the promoter (Madisen et al. 1998), and nuclear localization (Francastel et al. 1999). However, it is poorly understood which events in transactivation are the actual targets of long-range enhancer function at native gene loci.The murine ␤-globin gene locus is a model system for studying the molecular mechanisms of enhancer-dependent gene activation at a native locus. The locus contains embryonic and adult ␤-like globin genes that are ordered as they are expressed during development. Hig...

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Section: Nf-e2 and Pol II Recruitment To The ␤-Globin Promoter Are Lcmentioning

confidence: 99%

The β-globinlocus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation

Sawado¹,

Halow²,

Bender³

et al. 2003

Genes Dev.

164

166

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“…Targeted disruption of the p45/NF-E2 gene in mice revealed that NF-E2 is required for megakaryopoiesis (40), whereas studies in p45/ NF-E2-null CB3 erythroleukemia cells revealed an important role in activating ␤-globin transcription (32,33,41,42). We used complementation analysis in CB3 cells to show that NF-E2 establishes a component of the histone modification pattern of the murine ␤-globin locus.…”

mentioning

confidence: 99%

A WW Domain-binding Motif within the Activation Domain of the Hematopoietic Transcription Factor NF-E2 Is Essential for Establishment of a Tissue-specific Histone Modification Pattern

Kiekhaefer

Boyer

Johnson³

et al. 2004

Journal of Biological Chemistry

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Histone H3 methylated at lysine 4 (H3-meK4) co-localizes with hyperacetylated histones H3 and H4 in transcriptionally active chromatin, but mechanisms that establish H3-meK4 are poorly understood. Previously, we showed that the hematopoietic-specific activator NF-E2, which is required for ␤-globin transcription in erythroleukemia cells, induces histone H3 hyperacetylation and H3-meK4 at the adult ␤-globin genes (␤major and ␤minor). Chromatin immunoprecipitation analysis indicated that NF-E2 occupies hypersensitive site two (HS2) of the ␤-globin locus control region. The mechanism of NF-E2-mediated chromatin modification was investigated by complementation analysis in NF-E2-null CB3 erythroleukemia cells. The activation domain of the hematopoietic-specific subunit of NF-E2 (p45/NF-E2) contains two WW domainbinding motifs (PXY-1 and PXY-2). PXY-1 is required for activation of ␤-globin transcription. Here, we determined which step in NF-E2-dependent transactivation is PXY-1-dependent. A p45/NF-E2 mutant lacking 42 amino acids of the activation domain, including both PXY motifs, and a mutant lacking only PXY-1 were impaired in inducing histone H3 hyperacetylation, H3-meK4, and RNA polymerase II recruitment. The PXY motifs were not required for transactivation in the context of a GAL4 DNA-binding domain fusion to p45/NF-E2 in transient transfection assays. As the PXY-1 mutant occupied HS2 normally, the chromatin modification defect occurred post-DNA binding. PXY-1 was not required for recruitment of the histone acetyltransferases cAMP-responsive elementbinding protein-binding protein (CBP) and p300 to HS2. These results indicate that PXY-1 confers chromatinspecific transcriptional activation via interaction with a co-regulator distinct from CBP/p300 or by regulating CBP/p300 function.Mechanisms that dynamically regulate chromatin structure at localized sites and over broad chromosomal regions are crucial for controlling nuclear processes such as transcription. A common mode of regulating chromatin structure is the posttranslational modification of core histones, of which histone acetylation is the most extensively studied (1, 2). Hyperacetylated histones are often enriched in transcriptionally active chromatin (3, 4), although reductions in acetylation can occur upon transcriptional activation (5). Acetylation impacts transcription in part by increasing DNA accessibility within the nucleosome (6) and by perturbation of higher order chromatin folding (7,8).Analogous to acetylation, methylation of lysine 4 of histone H3 (H3-meK4) 1 marks transcriptionally active chromatin (9 -13). By contrast, histone H3 methylated at lysine 9 is associated with transcriptional repression (14 -16). At least one mechanism by which H3-meK4 functions is by inhibiting binding of the nucleosome remodeling deacetylase repressor complex to the amino-terminal tail of histone H3, thereby favoring the transcriptionally active state (17). Acetylated and methylated lysines within histones can also function as ligands to bind bromodomain-and chromo...

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“…Endogenous p45/NF-E2 occupies the LCR, and to a lesser extent, the bmajor promoter in erythroid cells (Daftari et al, 1999;Forsberg et al, 2000a;Johnson et al, 2001;Sawado et al, 2001;Im et al, 2005). The finding that Pol II occupies the LCR, but not the bmajor promoter, and p45/NF-E2 expression rescues Pol II occupancy at the promoter in CB3 cells, led to the model that p45/NF-E2 induces long-range Pol II transfer, resulting in considerably more Pol II at the promoter and transcriptional activation (Johnson et al, 2001).…”

Section: P45/nf-e2mentioning

confidence: 99%

Transcriptional control of erythropoiesis: emerging mechanisms and principles

Kim

2007

Oncogene

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Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells

Cited by 36 publications

References 47 publications

The β-globinlocus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation

The β-globinlocus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation

A WW Domain-binding Motif within the Activation Domain of the Hematopoietic Transcription Factor NF-E2 Is Essential for Establishment of a Tissue-specific Histone Modification Pattern

Transcriptional control of erythropoiesis: emerging mechanisms and principles

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