Distinct Mechanisms Control RNA Polymerase II Recruitment to a Tissue-Specific Locus Control Region and a Downstream Promoter

Johnson, Kirby D.; Christensen, Heather M.; Zhao, Bryan M.; Bresnick, Emery H.

doi:10.1016/s1097-2765(01)00309-4

Cited by 166 publications

(197 citation statements)

References 46 publications

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“…1A,B; Sawado et al 2001). Consistent with the observation that NF-E2 is required for pol II recruitment (Johnson et al 2001), high levels of pol II enrichment, as measured with an antibody that detects both phosphorylated and unphosphorylated forms, are detected only after induction. TFIIB, a component of the PIC, is enriched only 2.2-fold before induction, and this enrichment increases to 29.6-fold after induction (Fig.…”

Section: Transcription Factor Recruitment To the Promoter Correlates supporting

confidence: 74%

“…2001). In the ␤-globin locus, the Ser 5 phosphorylated form of CTD was shown to be enriched at the ␤ maj globin promoter after MEL cell induction (Johnson et al 2001). To determine if CTD phosphorylation is affected by the LCR, we performed an allele-specific ChIP analysis using an antibody against the phosphorylated CTD.…”

Section: The Lcr Functions Downstream Of Initiation Genes and Developmementioning

confidence: 99%

“…NF-E2 is composed of two subunits: p45 NF-E2 and p18 NF-E2 (Andrews et al 1993a(Andrews et al , 1993bChan et al 1993;Ney et al 1993), the latter of which is a member of the small Maf protein family, MafK (Igarashi et al 1994; for review, see Motohashi et al 1997). p45 NF-E2, which contains a transactivation domain, interacts with TAFII130 (Amrolia et al 1997) and CBP in vitro (Cheng et al 1997;Hung et al 2001) and is required for pol II recruitment to the ␤ maj globin gene promoter in mouse erythroleukemia (MEL) cells (Johnson et al 2001). Recently, we reported that NF-E2 binds to both the LCR and the ␤-globin promoter region, even though no canonical NF-E2 binding sites are present in the promoter (Sawado et al 2001).…”

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confidence: 99%

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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: Transcription Factor Recruitment To the Promoter Correlates supporting

confidence: 74%

Section: The Lcr Functions Downstream Of Initiation Genes and Developmementioning

confidence: 99%

mentioning

confidence: 99%

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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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“…(37) While the binding of p45/NF-E2 to HS2 is not required for the recruitment of pol II by LCR, it is required for proximal promoter acetylation and the recruitment of pol II by the adult beta-globin promoter. (38) This precise action of distal enhancer elements on promoters seems to need a direct contact, supporting the looping model. It also implies that the strand-breaking model and the looping model may involve different types of transcription factors.…”

Section: Chromatin Remodeling and Chromatin Domain Openingmentioning

confidence: 71%

A hypothesis for chromatin domain opening

Liu

Ling

2003

BioEssays

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SummaryThe eukaryotic genome is organized into different domains by cis-acting elements, such as boundaries/ insulators and matrix attachment regions, and is packaged with different degrees of condensation. In the M phase, the chromatin becomes further highly condensed into chromosomes. The first step for transcriptional activation of a given gene, at a particular time during development, in any locus, is the opening of its chromatin domain. This locus needs to be kept in this state in each early G 1 phase during every cell cycle. Certain distal enhance elements, including locus control regions (LCRs) and enhancers, are believed to perform this target chromatin domain opening process and several models have been proposed to explain distal enhance action. But they did not explain precisely how a given chromatin domain is opened. Based on various studies, we propose a hypothesis for the mechanism of opening chromatin on a large scale. One important mechanism may involved breaking one or two DNA strands and reducing the linking numbers within chromatin domain. The topological changes can overpass some complexes formed on DNA strands and can be transmitted from specific localized points over a broad region, until boundary elements or insulators are reached. These may initiate downstream events such as propagation of histone acetylation and the binding of transcription factors to proximal promoters and may further augment the action mediated by distal enhancer elements.

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“…RNA polymerase II is not associated to a promoter since the LCR does not contain any promoter. The RNA polymerase II stored at the LCR level might be transferred to the gene of the locus, which becomes open by the appropriate transcription factors [17]. The LCRs also contain an insulator, which has been more precisely located in the chicken b-globin locus.…”

Section: The Insulator Regionmentioning

confidence: 99%

Transgenesis for the study and the control of lactation

Houdebiné

Rival

Pantano³

et al. 2002

Reprod. Nutr. Dev.

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-The study and the control of milk synthesis are required to decipher the mechanisms of gene expression, to improve milk production, to modify milk composition, to induce a resistance to diseases in the mammary gland and to produce recombinant proteins of pharmaceutical interest. Transgenesis has become a mandatory tool to reach these goals. The use of transgenesis is still limited by the difficulty of adding foreign genes in farm animals and mainly by replacing genes by homologous recombination. Transgene expression is also often ill-controlled. The present paper summarizes the current progress in this field with a particular emphasis on expression vectors for transgenes. lactation / transgenesis / expression vectorsRésumé -La transgénèse pour l'étude et le contrôle de la lactation. L'étude et le contrôle de la synthèse du lait sont nécessaires pour décrypter les mécanismes de l'expression de gènes, pour amé-liorer la production de lait, pour modifier la composition du lait, pour induire une résistance de la glande mammaire contre des maladies infectieuses et pour produire des protéines recombinantes d'intérêt pharmaceutique. La transgénèse est devenue un outil indispensable pour mener à bien ces projets. La mise en oeuvre de la transgénèse est encore limitée par la difficulté d'ajouter des gènes étrangers chez les animaux d'élevage et surtout de remplacer des gènes par recombinaison homologue. L'expression des transgènes est par ailleurs souvent mal contrôlée. Cet article se propose de faire le point dans ce domaine en développant plus particulièrement la mise au point de vecteurs d'expression pour les transgènes. lactation / transgénèse / vecteurs d'expression

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Distinct Mechanisms Control RNA Polymerase II Recruitment to a Tissue-Specific Locus Control Region and a Downstream Promoter

Cited by 166 publications

References 46 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 hypothesis for chromatin domain opening

Transgenesis for the study and the control of lactation

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