Replication stress inhibits synthesis of histone mRNAs in yeast by removing Spt10p and Spt21p from the histone promoters

Bhagwat, Madhura; Nagar, Shreya; Kaur, Pritpal; Mehta, Riddhi; Vancurova, Ivana; Vančura, Aleš

doi:10.1016/j.jbc.2021.101246

Cited by 10 publications

(13 citation statements)

References 85 publications

(149 reference statements)

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“…2B). Consistent with previous studies ( 36, 37 ), we found that histone mRNAs in YPD have short half-lives, whereas ACT1 mRNA is more stable. Moreover, we showed that both histone and ACT1 mRNAs are significantly more stable in poor compared to rich nutrient conditions.…”

Section: Resultssupporting

confidence: 93%

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Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

Chatzitheodoridou

Bureik

Padovani

et al. 2023

Preprint

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To maintain protein homeostasis in changing nutrient environments, cells must precisely control the amount of their proteins, despite the accompanying changes in cell growth and biosynthetic capacity. As nutrients are major regulators of cell cycle length and progression, a particular challenge arises for the nutrient-dependent regulation of cell cycle genes, which are periodically expressed during the cell cycle. One important example are histones, which are needed at a constant histone-to-DNA stoichiometry. Here we show that budding yeast achieves histone homeostasis in different nutrients through a decoupling of transcript and protein abundance. We find that cells downregulate histone transcripts in poor nutrients to avoid toxic histone overexpression, but produce constant amounts of histone proteins through nutrient-specific regulation of translation efficiency. Our findings suggest that this allows cells to balance the need for rapid histone production under fast growth conditions with the tight regulation required to avoid toxic overexpression in poor nutrients.

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Section: Resultssupporting

confidence: 93%

“…Relative changes in mRNA concentrations were measured by RT-qPCR as described above. Target-specific primers were designed to bind to the HTB1, HTB2 and ACT1 coding sequences, respectively ( 36 ). The half-lives of histone and ACT1 mRNAs were calculated by fitting a single exponential function to the obtained mRNA decay curves.…”

Section: Methodsmentioning

confidence: 99%

Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

Chatzitheodoridou

Bureik

Padovani

et al. 2023

Preprint

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“…In S . cerevisiae, histone synthesis is inhibited following a DNA replication block with the treatment of hydroxyurea (HU) via a specific regulatory coupling (Bhagwat et al . 2021), which is likely mediated by the HIR complex ( hi stone regulatory genes ( HIR1 , HIR2 , HIR3 ) and h istone p eriodic c ontrol gene ( HPC2 )).…”

Section: Resultsmentioning

confidence: 99%

“…Tight control of the regulation of core histones throughout the cell cycle ensures the proper function of DNAtemplated processes (Eriksson et al 2012). Proper stoichiometry between nucleosomes and total DNA content is partly controlled through replication-coupled synthesis of histones (Robbins and Borun 1967), evidenced by experimental inhibition of DNA synthesis leading to rapid repression of histone synthesis (Osley 1991;Rattray and Müller 2012;Bhagwat et al 2021) Moreover, misexpression of histones outside of S-phase characteristically leads to cellular toxicity and growth arrest (Kurat et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Gene loss and cis-regulatory novelty shaped core histone gene evolution in the apiculate yeastHanseniaspora uvarum

Haase,

Steenwyk,

Boeke

2023

Preprint

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Across eukaryotic species, core histone genes display a remarkable diversity of cis-regulatory mechanisms despite their protein sequence conservation. However, the dynamics and significance of this regulatory turnover are not well understood. Here we describe the evolutionary history of core histone gene regulation across 400 million years in Saccharomycotina yeasts, revealing diverse lineage-specific solutions to core histone expression. We further characterize the emergence of a novel regulatory mode in the Hanseniaspora genus, which coincided with the loss of one copy of its paralogous core histones genes from its fast-evolving lineage. By analyzing the growth dynamics using live cell imaging of genetically modified Hanseniaspora uvarum, we observed a regulatory decoupling of core histone synthesis from DNA synthesis and propose that this may be adaptive for its rapid cell cycle progression. Overall, our findings imply that the frequent turnover of core histone cis-regulatory mechanisms likely provides distinct adaptive solutions for specific life histories.

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“…We found that CgSub2 interacted with H2A, with surplus-iron leading to a higher CgSub2-CgH2A interaction, despite a reduction in H2A levels (Fig 6C). Of note, decreased histone H2A levels under surplus-iron conditions may partly be due to general stress-responsive transcriptional downregulation of core histone genes in Cg, as the genotoxic stress is known to result in transcriptional downregulation of the histone H3 and H4 genes in Cg [47], and a reduction in histone mRNAs in S. cerevisiae [48]. Further, our co-immunoprecipitation results point towards the environment cue (iron abundance)responsive interaction of CgSub2 with the canonical histone H2A or the histone H2A variant CgHtz1, which may potentially modulate chromatin dynamics.…”

Section: Cgsub2 Is Essential For Surplus-iron-induced Host Adherencementioning

confidence: 99%

The Hog1 MAPK substrate governs Candida glabrata-epithelial cell adhesion via the histone H2A variant

Sahu,

Purushotham,

Kaur

2024

PLoS Genet

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CgHog1, terminal kinase of the high-osmolarity glycerol signalling pathway, orchestrates cellular response to multiple external stimuli including surplus-environmental iron in the human fungal pathogen Candida glabrata (Cg). However, CgHog1 substrates remain unidentified. Here, we show that CgHog1 adversely affects Cg adherence to host stomach and kidney epithelial cells in vitro, but promotes Cg survival in the iron-rich gastrointestinal tract niche. Further, CgHog1 interactome and in vitro phosphorylation analysis revealed CgSub2 (putative RNA helicase) to be a CgHog1 substrate, with CgSub2 also governing iron homeostasis and host adhesion. CgSub2 positively regulated EPA1 (encodes a major adhesin) expression and host adherence via its interactor CgHtz1 (histone H2A variant). Notably, both CgHog1 and surplus environmental iron had a negative impact on CgSub2-CgHtz1 interaction, with CgHTZ1 or CgSUB2 deletion reversing the elevated adherence of Cghog1Δ to epithelial cells. Finally, the surplus-extracellular iron led to CgHog1 activation, increased CgSub2 phosphorylation, elevated CgSub2-CgHta (canonical histone H2A) interaction, and EPA1 transcriptional activation, thereby underscoring the iron-responsive, CgHog1-induced exchange of histone partners of CgSub2. Altogether, our work mechanistically defines how CgHog1 couples Epa1 adhesin expression with iron abundance, and point towards specific chromatin composition modification programs that probably aid fungal pathogens align their adherence to iron-rich (gut) and iron-poor (blood) host niches.

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Replication stress inhibits synthesis of histone mRNAs in yeast by removing Spt10p and Spt21p from the histone promoters

Cited by 10 publications

References 85 publications

Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

Decoupling of transcript and protein concentrations ensures budding yeast histone homeostasis in different nutrient conditions

Gene loss and cis-regulatory novelty shaped core histone gene evolution in the apiculate yeastHanseniaspora uvarum

The Hog1 MAPK substrate governs Candida glabrata-epithelial cell adhesion via the histone H2A variant

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