scholarly journals BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

2021 ◽  
Author(s):  
Rafal Donczew ◽  
Steven Hahn
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Initiation ◽  
Family Members ◽  
Mechanisms Of Action ◽  
Histone H4 ◽  
Genome Wide ◽  
Acetylated Histone H4 ◽  
Basal Transcription Factors ◽  
Combined Defects ◽  
Target Transcription Factor

Human bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and processive elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

scholarly journals BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rafal Donczew ◽  
Steven Hahn
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Initiation ◽  
Family Members ◽  
Mechanisms Of Action ◽  
Histone H4 ◽  
Genome Wide ◽  
Acetylated Histone H4 ◽  
Basal Transcription Factors ◽  
Combined Defects ◽  
Target Transcription Factor

Human bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and early elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

scholarly journals Genome-Wide Relationships between TAF1 and Histone Acetyltransferases in Saccharomyces cerevisiae

2006 ◽  
Vol 26 (7) ◽  
pp. 2791-2802 ◽  
Author(s):  
Melissa Durant ◽  
B. Franklin Pugh
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Histone Acetyltransferases ◽  
Histone H4 ◽  
Promoter Regions ◽  
Genome Wide ◽  
Acetylated Histone H4

ABSTRACT Histone acetylation regulates gene expression, yet the functional contributions of the numerous histone acetyltransferases (HATs) to gene expression and their relationships with each other remain largely unexplored. The central role of the putative HAT-containing TAF1 subunit of TFIID in gene expression raises the fundamental question as to what extent, if any, TAF1 contributes to acetylation in vivo and to what extent it is redundant with other HATs. Our findings herein do not support the basic tenet that TAF1 is a major HAT in Saccharomyces cerevisiae, nor do we find that TAF1 is functionally redundant with other HATs, including Gcn5, Elp3, Hat1, Hpa2, Sas3, and Esa1, which is in contrast to previous conclusions regarding Gcn5. Our findings do reveal that of these HATs, only Gcn5 and Esa1 contribute substantially to gene expression genome wide. Interestingly, histone acetylation at promoter regions throughout the genome does not require TAF1 or RNA polymerase II, indicating that most acetylation is likely to precede transcription and not depend upon it. TAF1 function has been linked to Bdf1, which binds TFIID and acetylated histone H4 tails, but no linkage between TAF1 and the H4 HAT Esa1 has been established. Here, we present evidence for such a linkage through Bdf1.

scholarly journals Genome-wide mapping of histone H4 serine-1 phosphorylation during sporulation in Saccharomyces cerevisiae

2010 ◽  
Vol 38 (14) ◽  
pp. 4599-4606 ◽  
Author(s):  
Jérôme Govin ◽  
Jonathan Schug ◽  
Thanuja Krishnamoorthy ◽  
Jean Dorsey ◽  
Saadi Khochbin ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone H4 ◽  
Genome Wide

scholarly journals Reduced Gene Dosage of Histone H4 Prevents CENP-A Mislocalization in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Jessica R. Eisenstatt ◽  
Kentaro Ohkuni ◽  
Wei-Chun Au ◽  
Olivia Preston ◽  
Evelyn Suva ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromosomal Instability ◽  
Budding Yeast ◽  
Gene Dosage ◽  
Histone H3 ◽  
Histone H4 ◽  
Genome Wide ◽  
A Genome ◽  
Mutant Strains ◽  
Histone H3 Variant

ABSTRACTMislocalization of the centromeric histone H3 variant (Cse4 in budding yeast, CID in flies, CENP-A in humans) to non-centromeric regions contributes to chromosomal instability (CIN) in yeast, fly, and human cells. Overexpression and mislocalization of CENP-A has been observed in cancers, however, the mechanisms that facilitate the mislocalization of overexpressed CENP-A have not been fully explored. Defects in ubiquitin-mediated proteolysis of overexpressed Cse4 (GALCSE4) leads to its mislocalization and synthetic dosage lethality (SDL) in mutants for E3 ubiquitin ligases (Psh1, Slx5, SCFMet30, SCFCdc4), Doa1, Hir2, and Cdc7. In contrast, defects in sumoylation of GALcse4K215/216/A/R prevent its mislocalization and do not cause SDL in a psh1Δ strain. Here, we used a genome-wide screen to identify factors that facilitate the mislocalization of overexpressed Cse4 by characterizing suppressors of the psh1Δ GALCSE4 SDL. Deletions of histone H4 alleles (HHF1 or HHF2), which were among the most prominent suppressors, also suppress slx5Δ, cdc4-1, doa1Δ, hir2Δ, and cdc7-4 GALCSE4 SDL. Reduced dosage of H4 contributes to defects in sumoylation and reduced mislocalization of overexpressed Cse4. We determined that the hhf1-20, cse4-102, and cse4-111 mutants, which are defective in the Cse4-H4 interaction, also exhibit reduced sumoylation of Cse4 and do not display psh1Δ GALCSE4 SDL. In summary, we have identified genes that contribute to the mislocalization of overexpressed Cse4 and defined a role for the gene dosage of H4 in facilitating Cse4 sumoylation and mislocalization to non-centromeric regions, contributing to SDL when Cse4 is overexpressed in mutant strains.

scholarly journals Spt6 is required for the fidelity of promoter selection

2018 ◽  
Author(s):  
Stephen M. Doris ◽  
James Chuang ◽  
Olga Viktorovskaya ◽  
Magdalena Murawska ◽  
Dan Spatt ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromatin Structure ◽  
Genetic Information ◽  
Transcription Initiation ◽  
Elongation Factor ◽  
Initiation Site ◽  
Sequence Features ◽  
Coding Regions ◽  
Genome Wide ◽  
Site Competition

SUMMARYSpt6 is a conserved factor that controls transcription and chromatin structure across the genome. Although Spt6 is viewed as an elongation factor, spt6 mutations in Saccharomyces cerevisiae allow elevated levels of transcripts from within coding regions, suggesting that Spt6 also controls initiation. To address the requirements for Spt6 in transcription and chromatin structure, we have combined four genome-wide approaches. Our results demonstrate that Spt6 represses transcription initiation at thousands of intragenic promoters. We characterize these intragenic promoters, and find sequence features conserved with genic promoters. Finally, we show that Spt6 also regulates transcription initiation at most genic promoters and propose a model of initiation-site competition to account for this. Together, our results demonstrate that Spt6 controls the fidelity of transcription initiation throughout the genome and reveal the magnitude of the potential for expressing alternative genetic information via intragenic promoters.

scholarly journals Non-coding RNAs in Saccharomyces cerevisiae: what is the function?

2012 ◽  
Vol 40 (4) ◽  
pp. 907-911 ◽  
Author(s):  
Jian Wu ◽  
Daniela Delneri ◽  
Raymond T. O'Keefe
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Regulation ◽  
Mechanisms Of Action ◽  
Current Debate ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
Non Coding Rnas ◽  
Coding Capacity ◽  
Pervasive Transcription

New sequencing technologies and high-resolution microarray analysis have revealed genome-wide pervasive transcription in many eukaryotes, generating a large number of RNAs with no coding capacity. The focus of current debate is whether many of these ncRNAs (non-coding RNAs) are functional, and if so, what their function is. In this review, we describe recent discoveries in the field of ncRNAs in the yeast Saccharomyces cerevisiae. Newly identified ncRNAs in this budding yeast, their functions in gene regulation and possible mechanisms of action are discussed.

scholarly journals Reduced Gene Dosage of Histone H4 Prevents CENP-A Mislocalization and Chromosomal Instability in Saccharomyces cerevisiae

Genetics ◽  
2021 ◽  
Author(s):  
Jessica R Eisenstatt ◽  
Kentaro Ohkuni ◽  
Wei-Chun Au ◽  
Olivia Preston ◽  
Loran Gliford ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromosomal Instability ◽  
Budding Yeast ◽  
Gene Dosage ◽  
Histone H3 ◽  
Human Cells ◽  
Histone H4 ◽  
Genome Wide ◽  
A Genome ◽  
Histone H3 Variant

Abstract Mislocalization of the centromeric histone H3 variant (Cse4 in budding yeast, CID in flies, CENP-A in humans) to non-centromeric regions contributes to chromosomal instability (CIN) in yeast, fly, and human cells. Overexpression and mislocalization of CENP-A has been observed in cancers, however, the mechanisms that facilitate the mislocalization of overexpressed CENP-A have not been fully explored. Defects in proteolysis of overexpressed Cse4 (GALCSE4) leads to its mislocalization and synthetic dosage lethality (SDL) in mutants for E3 ubiquitin ligases (Psh1, Slx5, SCFMet30, SCFCdc4), Doa1, Hir2, and Cdc7. In contrast, defects in sumoylation of overexpressed cse4K215/216/A/R prevent its mislocalization and do not cause SDL in a psh1Δ strain. Here, we used a genome-wide screen to identify factors that facilitate the mislocalization of overexpressed Cse4 by characterizing suppressors of the psh1Δ GALCSE4 SDL. Deletions of histone H4 alleles (HHF1 or HHF2), which were among the most prominent suppressors, also suppress slx5Δ, cdc4-1, doa1Δ, hir2Δ, and cdc7-4 GALCSE4 SDL. Reduced dosage of H4 leads to defects in sumoylation and reduced mislocalization of overexpressed Cse4, which contributes to suppression of CIN when Cse4 is overexpressed. We determined that the hhf1-20, cse4-102, and cse4-111 mutants, which are defective in the Cse4-H4 interaction, also exhibit reduced sumoylation of Cse4 and do not display psh1Δ GALCSE4 SDL. In summary, we have identified genes that contribute to the mislocalization of overexpressed Cse4 and defined a role for the gene dosage of H4 in facilitating Cse4 sumoylation and mislocalization to non-centromeric regions, leading to CIN when Cse4 is overexpressed.

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