<scp>T</scp>rypanosoma brucei histone <scp>H</scp>1 inhibits <scp>RNA</scp> polymerase <scp>I</scp> transcription and is important for parasite fitness in vivo

Pena, Ana C.; Pimentel, Mafalda R.; Manso, Helena; Vaz‐Drago, Rita; Pinto‐Neves, Daniel; Aresta‐Branco, Francisco; Rijo‐Ferreira, Filipa; Guegan, Fabien; Coelho, Luís Pedro; Carmo‐Fonseca, Maria; Barbosa‐Morais, Nuno L.; Figueiredo, Luísa M.

doi:10.1111/mmi.12677

Cited by 24 publications

(37 citation statements)

References 74 publications

(118 reference statements)

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“…Similar de-repression of a promoter-proximal reporter gene was observed when the histone deacetylase DAC3 (Wang et al, 2010), the linker histone H1 (Povelones et al, 2012; Pena et al, 2014), or the nucleoplasmin-like protein NLP (Narayanan et al, 2011) was depleted. The function of DAC3 appears to be promoter-specific since expression of the VSG gene in the marked BES was unaffected at both the mRNA and the protein level (Wang et al, 2010).…”

Section: Factors Involved In Bes Transcription Regulationmentioning

confidence: 61%

“…Histone H1 is important for chromatin architecture and generally functions in chromatin condensation and transcription repression (Happel and Doenecke, 2009). Accordingly, co-silencing of the T. brucei H1 multigene family opened up chromatin globally with the strongest effect on silent BES promoters (Pena et al, 2014). Metabolic labeling of nascent RNA then showed that histone H1 depletion resulted in an approximately six-fold higher promoter-proximal transcription rate at a silent BES, indicating that relaxation of the nucleosome structure in the promoter region led to an increase of the transcription initiation rate at the silent BES (Pena et al, 2014).…”

Section: Factors Involved In Bes Transcription Regulationmentioning

confidence: 99%

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Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?

Günzl

Kirkham

Nguyen

et al. 2015

Gene

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Trypanosoma brucei is a vector borne, lethal protistan parasite of humans and livestock in sub-Saharan Africa. Antigenic Variation of its cell surface coat enables the parasite to evade adaptive immune responses and to live freely in the blood of its mammalian hosts. The coat consists of ten million copies of variant surface glycoprotein (VSG) that is expressed from a single VSG gene, drawn from a large repertoire and located near the telomere at one of fifteen so-called bloodstream expression sites (BESs). Thus, antigenic variation is achieved by switching to the expression of a different VSG gene. A BES is a tandem array of expression site-associated genes and a terminal VSG gene. It is polycistronically transcribed by a multifunctional RNA polymerase I (RNAPI) from a short promoter that is located 45–60 kb upstream of the VSG gene. The mechanism(s) restricting VSG expression to a single BES are not well understood. There is convincing evidence that epigenetic silencing and transcription attenuation play important roles. Furthermore, recent data indicated that there is regulation at the level of transcription initiation and that, surprisingly, the VSG mRNA appears to have a role in restricting VSG expression to a single gene. Here, we review BES expression regulation and propose a model in which telomere-directed, epigenetic BES silencing is opposed by BES promoter-directed, activated RNAPI transcription.

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Section: Factors Involved In Bes Transcription Regulationmentioning

confidence: 61%

Section: Factors Involved In Bes Transcription Regulationmentioning

confidence: 99%

Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?

Günzl

Kirkham

Nguyen

et al. 2015

Gene

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“…In addition, a broad range of chromatin proteins, remodellers and histone chaperones have now been shown to be involved in ES control. Knockdown of chromatin proteins and remodellers (ISWI, NLP, RAP1), histone chaperones (FACT, ASF1, CAF-1b), histone modifiers (DAC3, DOT1B), or histones H1 or H3 results in derepression of silent ES promoters or changes in VSG switching (Hughes et al ., 2007 ; Figueiredo et al ., 2008 ; Yang et al ., 2009 ; Denninger et al ., 2010 ; Wang et al ., 2010 ; Narayanan et al ., 2011 ; Alsford and Horn, 2012 ; Povelones et al ., 2012 ; Pena et al ., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

FACT plays a major role in histone dynamics affecting VSG expression site control in Trypanosoma brucei

Denninger

Rudenko

2014

Molecular Microbiology

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Chromatin remodelling is involved in the transcriptional regulation of the RNA polymerase I transcribed variant surface glycoprotein (VSG) expression sites (ESs) of Trypanosoma brucei. We show that the T. brucei FACT complex contains the Pob3 and Spt16 subunits, and plays a key role in ES silencing. We see an inverse correlation between transcription and condensed chromatin, whereby FACT knockdown results in ES derepression and more open chromatin around silent ES promoters. Derepressed ESs show increased sensitivity to micrococcal nuclease (MNase) digestion, and a decrease in histones at silent ES promoters but not telomeres. In contrast, FACT knockdown results in more histones at the active ES, correlated with transcription shut-down. ES promoters are derepressed in cells stalled at the G2/M cell cycle stage after knockdown of FACT, but not in G2/M cells stalled after knockdown of cyclin 6. This argues that the observed ES derepression is a direct consequence of histone chaperone activity by FACT at the G2/M cell cycle stage which could affect transcription elongation, rather than an indirect consequence of a cell cycle checkpoint. These experiments highlight the role of the FACT complex in cell cycle-specific chromatin remodelling within VSG ESs.

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“…Formaldehyde-assisted isolation of regulatory elements (FAIRE) was performed essentially as described previously (Pena et al 2014). In brief, a total of 1.2 9 10 8 cells were fixed for 10 min in 1% PFA in PBS.…”

Section: Faire Techniquementioning

confidence: 99%

The Trypanosoma brucei RNA‐Binding Protein TbRRM1 is Involved in the Transcription of a Subset of RNA Pol II‐Dependent Genes

Bañuelos

Levy

Níttolo

et al. 2019

J Eukaryotic Microbiology

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It has been long thought that RNA Polymerase (Pol) II transcriptional regulation does not operate in trypanosomes. However, recent reports have suggested that these organisms could regulate RNA Pol II transcription by epigenetic mechanisms. In this paper, we investigated the role of TbRRM1 in transcriptional regulation of RNA Pol II‐dependent genes by focusing both in genes located in a particular polycistronic transcription unit (PTU) and in the monocistronic units of the SL‐RNA genes. We showed that TbRRM1 is recruited throughout the PTU, with a higher presence on genes than intergenic regions. However, its depletion leads both to the decrease of nascent RNA and to chromatin compaction only of regions located distal to the main transcription start site. These findings suggest that TbRRM1 facilitates the RNA Pol II transcriptional elongation step by collaborating to maintain an open chromatin state in particular regions of the genome. Interestingly, the SL‐RNA genes do not recruit TbRRM1 and, after TbRRM1 knockdown, nascent SL‐RNAs accumulate while the chromatin state of these regions remains unchanged. Although it was previously suggested that TbRRM1 could regulate RNA Pol II‐driven genes, we provide here the first experimental evidence which involves TbRRM1 to transcriptional regulation.

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Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo

Cited by 24 publications

References 74 publications

Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?

Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?

FACT plays a major role in histone dynamics affecting VSG expression site control in Trypanosoma brucei

The Trypanosoma brucei RNA‐Binding Protein TbRRM1 is Involved in the Transcription of a Subset of RNA Pol II‐Dependent Genes

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