Tight cooperation between Mot1p and NC2β in regulating genome-wide transcription, repression of transcription following heat shock induction and genetic interaction with SAGA

Spedale, Gianpiero; Meddens, Claartje A.; Koster, Maria J.E.; Ko, Cheuk W.; Hooff, Sander R. van; Holstege, Frank C.P.; Timmers, H. Th. Marc; Pijnappel, W.W.M. Pim

doi:10.1093/nar/gkr784

Cited by 16 publications

(31 citation statements)

References 47 publications

(105 reference statements)

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“…The differential sensitivity of TATA-containing versus TATA-less promoters may be attributable to their regulation by different coactivator complexes. The SAGA complex loads TBP onto TATA-containing promoters (47) and is also associated with high TBP turnover (40), suggesting that it synergizes with Mot1 in TBP removal, a hypothesis supported by the finding of negative genetic interaction between Mot1 and SAGA (17). In contrast, TATA-less promoters tend to be regulated by the TFIID coactivator complex (47).…”

Section: Discussionmentioning

confidence: 97%

“…Presumably, loss of TBP at TATA-less promoters would result in decreased expression of the associated genes, while gain of TBP at TATA-containing promoters would increase gene expression. Indeed, it has been shown that AA-mediated depletion of Mot1 tends to reduce the expression of TATA-less genes (17). To ascertain the biological significance of changes in TBP binding that occur when Mot1 is inactivated, we plotted the change in TBP occupancy at promoters as a heat map ranked by the expression of the associated gene in the mot1-42 mutant strain versus control (16).…”

Section: Global Mapping Of Mot1 and Tbp On Native Chromatinmentioning

confidence: 99%

“…However, numerous transcriptional profiling studies have established that loss of Mot1 both increases and decreases gene expression (4,5,(11)(12)(13)(14)(15)(16)(17)(18). Furthermore, loss of Mot1 has also been found to reduce TBP association with some promoters (11, 12, 18-21).…”

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confidence: 99%

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Mot1 Redistributes TBP from TATA-Containing to TATA-Less Promoters

Zentner

Henikoff

2013

Molecular and Cellular Biology

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The Swi2/Snf2 family ATPase Mot1 displaces TATA-binding protein (TBP) from DNA in vitro, but the global relationship between Mot1 and TBP in vivo is unclear. In particular, how Mot1 activates transcription is poorly understood. To address these issues, we mapped the distribution of Mot1 and TBP on native chromatin at base pair resolution. Mot1 and TBP binding sites coincide throughout the genome, and depletion of TBP results in a global decrease in Mot1 binding. We find evidence that Mot1 approaches TBP from the upstream direction, consistent with its in vitro mode of action. Strikingly, inactivation of Mot1 leads to both increases and decreases in TBP-genome association. Sites of TBP gain tend to contain robust TATA boxes, while sites of TBP loss contain poly(dA-dT) tracts that may contribute to nucleosome exclusion. Sites of TBP gain are associated with increased gene expression, while decreased TBP binding is associated with reduced gene expression. We propose that the action of Mot1 is required to clear TBP from intrinsically preferred (TATA-containing) binding sites, ensuring sufficient soluble TBP to bind intrinsically disfavored (TATA-less) sites.T ATA-binding protein (TBP) is a general regulator of eukaryotic transcription required for initiation by all three eukaryotic RNA polymerases (1). TBP lies at the center of a complex transcriptional network (2) and as such is regulated by a diverse array of factors. One such TBP-regulating protein is modifier of transcription 1 (Mot1), a highly conserved (3) and essential (4, 5) member of the Swi2/Snf2 ATPase family. Mot1 uses the energy derived from ATP hydrolysis to remove TBP from DNA (6), and the mechanism of action of Mot1 is perhaps the best understood of all Swi2/Snf2-like ATPases. Mot1 recognizes TBP from upstream, associating with TBP from above via its acidic loops. The Swi2/Snf2 ATPase domain of Mot1 contacts DNA ϳ17 bp upstream of TBP and translocates toward TBP, loosening its association of TBP with DNA. Last, the latch of Mot1 occupies the DNAbinding groove of TBP, displacing the Mot1-TBP complex from DNA and preventing TBP from rebinding DNA (7-10).The finding that Mot1 displaces TBP from DNA (6) led to the hypothesis that it would act primarily as a transcriptional repressor. However, numerous transcriptional profiling studies have established that loss of Mot1 both increases and decreases gene expression (4,5,(11)(12)(13)(14)(15)(16)(17)(18). Furthermore, loss of Mot1 has also been found to reduce TBP association with some promoters (11, 12, 18-21). Several models have been put forward to reconcile these findings with the well-characterized TBP-displacing activity of Mot1: (i) a preinitiation complex (PIC) remodeling model, wherein Mot1 alters the PIC conformation, presumably via interaction with TBP followed by ATP hydrolysis and translocation, to enhance transcriptional permissiveness (13); (ii) a PIC formation model, wherein the TBP-Mot1 complex nucleates an alternative, transcriptionally competent PIC (22); (iii) a nucleosome remodeling mode...

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Section: Discussionmentioning

confidence: 97%

Section: Global Mapping Of Mot1 and Tbp On Native Chromatinmentioning

confidence: 99%

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Mot1 Redistributes TBP from TATA-Containing to TATA-Less Promoters

Zentner

Henikoff

2013

Molecular and Cellular Biology

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“…The select validation of the enrichment of Ncb2 data points that the higher occupancy of the regulator does not necessarily result in the transcriptional activation as the expression of several genes was also repressed. Notwithstanding, the dual role of Ncb2, the genome-wide occupancy profiling reaffirmed its role as a global regulator of gene expression4660.…”

Section: Discussionmentioning

confidence: 90%

The global regulator Ncb2 escapes from the core promoter and impacts transcription in response to drug stress in Candida albicans

Shariq

Dhamgaye

Nair

et al. 2017

Sci Rep

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Ncb2, the β subunit of NC2 complex, a heterodimeric regulator of transcription was earlier shown to be involved in the activated transcription of CDR1 gene in azole resistant isolate (AR) of Candida albicans. This study examines its genome-wide role by profiling Ncb2 occupancy between genetically matched pair of azole sensitive (AS) and AR clinical isolates. A comparison of Ncb2 recruitment between the two isolates displayed that 29 genes had higher promoter occupancy of Ncb2 in the AR isolate. Additionally, a host of genes exhibited exclusive occupancy of Ncb2 at promoters of either AR or AS isolate. The analysis also divulged new actors of multi-drug resistance, whose transcription was activated owing to the differential occupancy of Ncb2. The conditional, sequence-specific positional escape of Ncb2 from the core promoter in AS isolate and its preferential recruitment to the core promoter of certain genes in AR isolates was most noteworthy means of transcription regulation. Together, we show that positional rearrangement of Ncb2 resulting in either activation or repression of gene expression in response to drug-induced stress, represents a novel regulatory mechanism that opens new opportunities for therapeutic intervention to prevent development of drug tolerance in C. albicans cells.

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“…Promoter sequences contain TFBS that recruit (TFs) and assemble the transcription preinitiation complex that guides RNA polymerase II to the transcription start site 47. The location of promoters relative to genes, usually located just upstream of a gene, has facilitated their identification and annotation (figure 1A).…”

Section: Dna Regulatory Elementsmentioning

confidence: 99%

Non-coding DNA in IBD: from sequence variation in DNA regulatory elements to novel therapeutic potential

Meddens

List

Nieuwenhuis

et al. 2019

Gut

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Genome-wide association studies have identified over 200 loci associated with IBD. We and others have recently shown that, in addition to variants in protein-coding genes, the majority of the associated loci are related to DNA regulatory elements (DREs). These findings add a dimension to the already complex genetic background of IBD. In this review we summarise the existing evidence on the role of DREs in IBD. We discuss how epigenetic research can be used in candidate gene approaches that take non-coding variants into account and can help to pinpoint the essential pathways and cell types in the pathogenesis of IBD. Despite the increased level of genetic complexity, these findings can contribute to novel therapeutic options that target transcription factor binding and enhancer activity. Finally, we summarise the future directions and challenges of this emerging field.

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Tight cooperation between Mot1p and NC2β in regulating genome-wide transcription, repression of transcription following heat shock induction and genetic interaction with SAGA

Cited by 16 publications

References 47 publications

Mot1 Redistributes TBP from TATA-Containing to TATA-Less Promoters

Mot1 Redistributes TBP from TATA-Containing to TATA-Less Promoters

The global regulator Ncb2 escapes from the core promoter and impacts transcription in response to drug stress in Candida albicans

Non-coding DNA in IBD: from sequence variation in DNA regulatory elements to novel therapeutic potential

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