Chromatin interaction mechanism of transcriptional control invivo

Gribnau, Joost; Boer, Ernie de; Trimborn, Tolleiv; Wijgerde, Mark; Milot, Éric; Grosveld, Frank; Fraser, Peter

doi:10.1093/emboj/17.20.6020

Cited by 90 publications

(74 citation statements)

References 44 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1B). Consistent with our earlier work (Gribnau et al 1998), the RNAPII elongation inhibitor DRB pro- Article is online at …”

supporting

confidence: 89%

“…In this study we assessed RNAPII localization during short-term transcription inhibition to investigate these possibilities. DRB (5,6-Dichlorobenzimidazole 1-␤-D-ribofuranoside) specifically inhibits RNAPII elongation by inhibiting kinases that phosphorylate Ser2 of the C-terminal domain (CTD) of the large subunit of RNAPII (Fraser et al 1978;Marshall and Price 1995;Marshall et al 1996;Gribnau et al 1998). Heat shock at 45°C has been shown to globally inhibit transcription, disrupting both initiation and elongation (Hieda et al 2005).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transcription factories are nuclear subcompartments that remain in the absence of transcription

Mitchell¹,

Fraser²

2008

Genes Dev.

221

196

View full text Add to dashboard Cite

Nascent transcription occurs at nuclear foci of concentrated, hyperphosphorylated RNA polymerase II (RNAPII). We investigate RNAPII localization, distal gene coassociation, and Hbb locus conformation during inhibition of transcription. Our results show distal active genes remain associated with RNAPII foci and each other in the absence of elongation. When initiation is inhibited, active genes dissociate from RNAPII foci and each other, suggesting initiation is necessary to tether distal active genes to shared foci. In the absence of transcription RNAPII foci remain, indicating they are not simple accumulations of RNAPII on transcribed genes but exist as independent nuclear subcompartments. Transcription is a fundamental, life-essential process, yet we lack a clear picture of how and where it occurs in vivo. Textbooks tell us that RNA polymerase II (RNAPII) is recruited to the promoters of genes when they become active, suggesting that transcription sites form de novo on individual genes. However, nascent transcription in the nucleus occurs within a limited number of discrete foci containing high concentrations of active RNAPII, termed transcription factories (Jackson et al. 1993;Wansink et al. 1993). Previously, we showed that the Hbb genes are often transcribed in the same factory as other erythroid expressed genes, separated by tens of megabases in cis (Eraf and Uros) or in trans (Hba) (Osborne et al. 2004). This has been confirmed by recent 4C (chromosome conformation capture-on-chip) studies showing associations between Hbb and multiple active genes (Simonis et al. 2006). Furthermore, several studies have shown that individual genes often loop out of their chromosomal territory upon activation, suggesting repositioning commonly occurs with transcriptional activation (Volpi et al. 2000;Chambeyron and Bickmore 2004;Wiblin et al. 2005). Indeed, we showed recently that immediate early gene activation occurs via rapid gene repositioning to preassembled transcription factories (Osborne et al. 2007). Taken together, these data suggest that genes migrate to pre-existing specialized sites in the nucleus for transcription.However, whether transcription factories are simply aggregates of RNAPII on individual active genes or independent structures is still unclear. In this study we assessed RNAPII localization during short-term transcription inhibition to investigate these possibilities. DRB (5,6-Dichlorobenzimidazole 1-␤-D-ribofuranoside) specifically inhibits RNAPII elongation by inhibiting kinases that phosphorylate Ser2 of the C-terminal domain (CTD) of the large subunit of RNAPII (Fraser et al. 1978;Marshall and Price 1995;Marshall et al. 1996;Gribnau et al. 1998). Heat shock at 45°C has been shown to globally inhibit transcription, disrupting both initiation and elongation (Hieda et al. 2005). In mammalian cells, heatshock-induced inhibition of RNAPII occurs specifically through production of B2 RNAs (transcribed from short interspersed elements [SINEs] by RNA polymerase III) that bind to RNAPII preinitiation com...

show abstract

“…1B). Consistent with our earlier work (Gribnau et al 1998), the RNAPII elongation inhibitor DRB pro- Article is online at …”

supporting

confidence: 89%

mentioning

confidence: 99%

Transcription factories are nuclear subcompartments that remain in the absence of transcription

Mitchell¹,

Fraser²

2008

Genes Dev.

221

196

View full text Add to dashboard Cite

show abstract

“…The role of NF-Y might instead be less direct, by modifying how the enhancers interact with the albumin promoter. Studies have suggested cycling of the distant LCR among the ⑀, ␥, and ␤ globin genes (23,24,65), and such cycling may occur in our dual promoter model. In the absence of NF-Y, dissociation of enhancer-promoter complexes during cycling might be slowed, which could reduce activity from both promoters.…”

Section: Discussionmentioning

confidence: 71%

“…Such behavior is not observed with plasmid models of the ␤-globin locus, where promoters compete for a common enhancer. These models combine normally distant transcription regulatory modules and so deal with only a limited aspect of long distance regulation in the ␤-globin locus (23,24). Nevertheless, the plasmid models establish two important properties of the promoters.…”

mentioning

confidence: 99%

Distant Enhancers Stimulate the Albumin Promoter through Complex Proximal Binding Sites

Vorachek

Steppan

Lima

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

The albumin-␣-fetoprotein locus epitomizes the main features of transcriptional regulation of fetal and adult hepatocyte-specific genes: developmentally regulated promoters and strong distant enhancers. Full enhancer activity required only a proximal albumin-promoter region containing the TATA box, hepatic nuclear factor 1 (HNF1), and nuclear factor Y (NF-Y) sites. Deletion of the HNF1 site abrogated enhancer and promoter activity, whereas methylation of the site reduced all activity by about 3-fold. Deletion of the NF-Y site attenuated activity by about half, but much of the activity could be replaced by juxtaposition of an upstream region (designated distal element IV). Gel shift and competition analysis demonstrated that binding of architectural factors overlapped NF-Y binding. Moreover, a mutation that eliminated NF-Y binding but only minimally perturbed the surrounding region did not affect enhancer function. In plasmids with a second promoter, the enhancers simultaneously stimulated both albumin and ␣-fetoprotein promoters with minimal competition, but surprisingly some mutations in the albumin promoter attenuated expression from both promoters, whereas another uncoupled their expression. With single promoters, the function of the proximal promoter region was controlled by three parameters in the following hierarchy: HNF1 binding > local architecture > NF-Y binding, but integrated two-promoter function had a much greater dependence on NF-Y.

show abstract

“…In support of this, it has been shown that in transgenic mice harboring the human ␤-globin locus, while most cells in the fetal liver possess mRNA for both ␥ and ␤-globin, only a relatively small proportion display unspliced primary transcripts indicative of ongoing transcription of both genes (Wijgerde et al 1995). Further experiments have utilized DRB, a reversible inhibitor of transcriptional elongation (Gribnau et al 1998;Trimborn et al 1999). Upon release of fetal liver cells from DRB inhibition, a reproducible lag is observed in the reappearance of double signals, as compared to single signals indicating transcription from a single globin gene.…”

Section: How Do Lcrs and Enhancers Mediate Gene Activation Genes And Dementioning

confidence: 97%

Looping versus linking: toward a model for long-distance gene activation

Bulger¹,

Groudine²

1999

Genes & Development

412

278

View full text Add to dashboard Cite

Chromatin interaction mechanism of transcriptional control invivo

Cited by 90 publications

References 44 publications

Transcription factories are nuclear subcompartments that remain in the absence of transcription

Transcription factories are nuclear subcompartments that remain in the absence of transcription

Distant Enhancers Stimulate the Albumin Promoter through Complex Proximal Binding Sites

Looping versus linking: toward a model for long-distance gene activation

Contact Info

Product

Resources

About