Control of eukaryotic gene expression: Gene loops and transcriptional memory

Hampsey, Michael; Singh, Bharat; Ansari, Athar; Lainé, Jean; Krishnamurthy, Shankarling

doi:10.1016/j.advenzreg.2010.10.001

Cited by 86 publications

(103 citation statements)

References 33 publications

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“…This might be consistent with recent findings concerning the role of PPAR-␦ as an activator of ␤-catenin transcription activity (29). Taken together, these data support the idea of required regulatory chromatin looping to activate VEGFA gene transcription, as suggested in the "chromatin hub model" (64), which might lead to ␤-catenin-mediated chromatin regulation as a general mechanism for other Wnt target genes (35,65).…”

Section: Discussionsupporting

confidence: 91%

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

Hwang

Kim

Jeong

2012

Journal of Biological Chemistry

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Background: Mechanism of VEGFA transcription by complex interplay of ␤-catenin and PPAR-␦ remains elusive. Results: The VEGFA promoter was dynamically occupied by ␤-catenin, TCF-4, and PPAR-␦. ␤-Catenin also bound downstream region of the VEGFA gene. Conclusion: ␤-Catenin is responsible for the formation of chromatin loops, which is relieved by PPAR-␦ activation. Significance: Proposed mechanism could provide clues for VEGFA-mediated colon cancer cell initiation.

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Section: Discussionsupporting

confidence: 91%

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

Hwang

Kim

Jeong

2012

Journal of Biological Chemistry

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“…Several studies have linked TFIIB with transcription reinitiation events, where TFIIB interacts with the components of transcription termination and polyadenylation complexes cleavage and polyadenylation specificity factor (CPSF) and CstF, which localize to both the gene-promoter and 3′-processing site (4)(5)(6)19). We have shown that phosphorylation of TFIIB ser-65 is crucial for its interaction with CstF-64 and its recruitment to the gene-promoter and 3′-processing site (7).…”

Section: Tfiib Phosphorylation Is Reduced Upon Treatment Of Cells Withmentioning

confidence: 98%

“…It has emerged in recent years that TFIIB also engages in contact with factors that are involved in transcription termination and facilitates the formation of loops between the gene promoter and terminator (4)(5)(6). The highly conserved Bfinger/reader region of TFIIB plays critical role(s) in transcription initiation, promoter-terminator contacts, and also transcriptional activation, suggesting that these events are linked (1).…”

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confidence: 99%

TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response

Shandilya

Wang

Roberts

2012

Proc. Natl. Acad. Sci. U.S.A.

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The general transcription factor II B (TFIIB) plays a central role in both the assembly of the transcription complex at gene promoters and also in the events that lead to transcription initiation. TFIIB is phosphorylated at serine-65 at the promoters of several endogenous genes, and this modification is required to drive the formation of gene promoter-3′ processing site contacts through the cleavage stimulation factor 3′ (CstF 3′)-processing complex. Here we demonstrate that TFIIB phosphorylation is dispensable for the transcription of genes activated by the p53 tumor suppressor. We find that the kinase activity of TFIIH is critical for the phosphorylation of TFIIB serine-65, but it is also dispensable for the transcriptional activation of p53-target genes. Moreover, we demonstrate that p53 directly interacts with CstF independent of TFIIB phosphorylation, providing an alternative route to the recruitment of 3′-processing complexes to the gene promoter. Finally, we show that DNA damage leads to a reduction in the level of phospho-ser65 TFIIB that leaves the p53 transcriptional response intact, but attenuates transcription at other genes. Our data reveal a mode of phospho-TFIIB-independent transcriptional regulation that prioritizes the transcription of p53-target genes during cellular stress.T he general transcription factor TFIIB plays a central role in the assembly of the transcription complex at the gene promoter (1-3). It has emerged in recent years that TFIIB also engages in contact with factors that are involved in transcription termination and facilitates the formation of loops between the gene promoter and terminator (4-6). The highly conserved Bfinger/reader region of TFIIB plays critical role(s) in transcription initiation, promoter-terminator contacts, and also transcriptional activation, suggesting that these events are linked (1).We recently reported that TFIIB is phosphorylated at ser-65 at the promoters of several endogenous genes and that this event is required for productive transcription (7). Moreover, phosphorylation of TFIIB ser-65 directly augments the interaction between TFIIB and the CstF complex and facilitates promoter-3′ processing site contacts. Whether or not these events are universally required for the transcription of genes by RNA polymerase II (RNAPII) is not known.Recent years have seen the emergence of multiple and distinct pathways to transcription (8-11). In this regard, the posttranslational modifications of the RNAPII carboxyl-terminal domain (CTD), specifically phosphorylation, and the enzymes responsible have revealed new gene-specific pathways in transcription control. This is particularly evident at p53-responsive genes, which require distinct events to ensure that the target genes involved in stressresponse pathways are robustly and rapidly induced under suboptimal cellular conditions (12-16).In this study we demonstrate that the phosphorylation of TFIIB ser-65 is not universally required for transcription, and that target genes under the control of p53 can bypass this ...

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“…139,140 Interestingly, recent studies investigating the regulation of the BRCA1 promoter have identified gene loop structures with intron sequences. 141 Gene loops are transient structures formed by juxtaposition of the promoter and terminator region [142][143][144] that can contribute to transcriptional regulation by facilitating the re-cycling of the polymerase [144][145][146] and enhance transcriptional directionality. 147 If the bi-directional hnRNPA1 and CBX5 promoter structure also uses gene loop structures for fine tuning of transcriptional regulation will be an intriguing question for future analyses by chromosome conformation methodologies.…”

Section: Genetic Regulation Of Cbx5 Transcriptionmentioning

confidence: 99%

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

Vad-Nielsen

Nielsen

2015

Cancer Biology & Therapy

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H eterochromatin protein 1a (HP1a) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di-or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1a has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1a serves a unique biological role in breast cancer related processes and in particular for epigenetic control mechanisms involved in aberrant cell proliferation and metastasis. However, how HP1a deregulation plays dual mechanistic functions for cancer cell proliferation and metastasis suppression and the underlying cellular mechanisms are not yet comprehensively described. In this paper we provide an overview of the role of HP1a as a new sight of epigenetics in proliferation and metastasis of human breast cancer. This highlights the importance of addressing HP1a in breast cancer diagnostics and therapeutics.

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Control of eukaryotic gene expression: Gene loops and transcriptional memory

Cited by 86 publications

References 33 publications

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

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