Coordination of PIC Assembly and Chromatin Remodeling During Differentiation-Induced Gene Activation

Soutoglou, Evi; Talianidis, Iannis

doi:10.1126/science.1068356

Cited by 293 publications

(263 citation statements)

References 26 publications

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“…Blocking Brg1 or SWI/SNF activity interferes with differentiation in retinal, myeloid, muscle, adipocyte, enterocyte, erythrocyte and neuronal cells. 31,[74][75][76][77][78][79][80] Together, the observations above suggest that the antagonistic interactions between Geminin and SWI/SNF that we have observed during neurogenesis could also regulate the proliferative-differentiative transition in other cellular contexts. Effects of both Geminin and SWI/SNF in regulating the proliferation to differentiation transition intersect with many other critical cell cycle and transcriptional control systems in a complex manner.…”

Section: Geminin Swi/snf and Regulation Of The Cell Proliferation-dmentioning

confidence: 72%

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

Seo

Kroll²

2006

Cell Cycle

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Section: Geminin Swi/snf and Regulation Of The Cell Proliferation-dmentioning

confidence: 72%

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

Seo

Kroll²

2006

Cell Cycle

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“…Upon activation by heat shock, Pol II is able to rapidly transcribe these genes. Regulation of Pol II activity after recruitment has also been described in bacteria 23 , yeast 13 and mammalian cell lines 3,[6][7][8][9][10][11][12] , and includes instances where Pol II is found in an inactive pre-initiation complex 24,25 . We will collectively refer to inactive Pol II near the transcription start site as stalled Pol II.…”

Section: Introductionmentioning

confidence: 96%

RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo

et al. 2007

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It is widely assumed that the key rate-limiting step in gene activation is the recruitment of RNA polymerase II (Pol II) to the core promoter 2 . Although there are well-documented examples where Pol II is recruited to a gene but stalls3 -14, a general role for Pol II stalling in development has not been established. We have performed comprehensive Pol II ChIP-chip assays in Drosophila embryos and identified three distinct Pol II binding behaviors: active (uniform binding across the entire transcription unit), no binding, and stalled (binding at the transcription start site). The striking feature of the ~10% genes that are stalled is that they are highly enriched for developmental control genes that are repressed at the time of analysis or poised for activation during subsequent stages of development. We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development.Pol II stalling is probably best studied at heat shock genes in Drosophila, where Pol II engages in transcription but pauses immediately downstream of the transcriptional start site 3,4,22 . Upon activation by heat shock, Pol II is able to rapidly transcribe these genes. Regulation of Pol II activity after recruitment has also been described in bacteria 23 , yeast 13 and mammalian cell lines 3,[6][7][8][9][10][11][12] , and includes instances where Pol II is found in an inactive pre-initiation complex 24,25 . We will collectively refer to inactive Pol II near the transcription start site as stalled Pol II.To determine at which genes Pol II stalling occurs during development, we analyzed global Pol II occupancy in whole Drosophila embryos. While this is one of the few systems where The results show that many genes known to be repressed in Toll 10b embryos display strikingly high levels of Pol II near the transcription start site (Fig.1A-D). In some cases the prominent Pol II peak is tightly restricted to the promoter region (e.g. at the tup gene in Fig. 1A), while at other genes Pol II is also found at low levels throughout the transcription unit (e.g. the sog and brk genes Fig. 1C,D). This is consistent with previous evidence that some genes such as sog are transiently activated but then repressed at later stages 26 , while other genes such as tup are never activated in Toll 10b mutants 19,20 .The Pol II profile of repressed genes is clearly distinct from those of active genes ( Fig. 1E, F). For example, the Hbr gene, which encodes an FGF receptor specifically expressed in mesodermal precursors ( Fig. 1E), and ribosomal genes such as RpL3 (Fig.1F), show uniformly high levels of Pol II throughout the transcription unit. Furthermore, genes that are silent in the early embryo simply lack Pol II binding altogether ( Fig. 1G, H). Thus, there appears to be three distinct classes of genes: those with Pol II distributed throughout the transcription unit, those genes with preferential enrichment of Pol II at the transcription site, and genes that lack Pol II binding altogether.To further characterize t...

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“…Also, GTFs bind to Drosophila promoters that are repressed by Polycomb group proteins (Breiling et al 2001). It has been shown that chromatin remodeling of the ␣1-antitrypsin gene promoter occurs after PIC assembly (Soutoglou and Talianidis 2002), and that elongation is the rate-limiting step in the regulation of many genes, including c-myc (Bentley and Groudine 1986;Krumm et al 1992), c-fos (Plet et al 1995), heat-shock protein (Brown et al 1996;Lis 1998), and transcription regulated by the HIV-1 LTR (Marciniak and Sharp 1991; for review, see Jones and Peterlin 1994). These observations demonstrate that events downstream of PIC assembly can be rate-limiting steps in transcription, and may represent common mechanisms for establishing an active state in many genes.…”

Section: Relationship Between Expression Levels and Pic Assemblymentioning

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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Coordination of PIC Assembly and Chromatin Remodeling During Differentiation-Induced Gene Activation

Cited by 293 publications

References 26 publications

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo

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

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