Roles for H2A.Z and Its Acetylation in GAL1 Transcription and Gene Induction, but Not GAL1-Transcriptional Memory

Halley, Jeffrey E.; Kaplan, Tommy; Wang, Alice Y.; Kobor, Michæl S.; Rine, Jasper

doi:10.1371/journal.pbio.1000401

Cited by 79 publications

(108 citation statements)

References 39 publications

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“…Histone H2A.Z is strongly implicated in the activation of transcription initiation (19,30,32,34,92,99). The results of the experiments reported here argue that H2A.Z also influences one or more steps in transcription elongation.…”

Section: Discussionmentioning

confidence: 57%

“…We also assessed the negative impact of the SWR1 complex on elongation phenotypes in the absence of its normal Htz1 substrates (32,68). The deletion of SWR1 is partially able to suppress the sensitivity of htz1⌬ cells to 6-AU and MPA (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although Htz1 is generally concentrated at promoters genome wide, it is not entirely absent from ORFs and can actually be enriched within the ORFs of individual genes (2,32,39,100). Acetylated Htz1-K14ac has also been observed over the ORF and positively correlates with the level of transcription (66).…”

Section: Discussionmentioning

confidence: 99%

“…The X-ray crystal structure of nucleosomes containing H2A.Z has been determined and, together with the results of biochemical experiments, argues that H2A.Z alters the physical properties of the chromatin template (7). Histone H2A.Z is itself subject to posttranslational modifications, including acetylation, ubiquitylation, and sumoylation, and these may alter its chromatin association, exchange dynamics, structure, and function (8,32,39,41,43,66,81,84,95). H2A.Z is broadly but nonuniformly distributed throughout the chromosomes and is deposited by specific remodeling complexes, such as the yeast SWR1 complex (SWR1) (3,45,51,60,67).…”

mentioning

confidence: 99%

“…H2A.Z has important functions during transcription initiation (19,30,32,34,92,99). Early experiments in budding yeast revealed that Htz1 is partially redundant with the Swi/Snf nucleosome remodeling and SAGA histone modification complexes, providing genetic evidence for a role in transcription activation.…”

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confidence: 99%

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Histone Variant H2A.Z and RNA Polymerase II Transcription Elongation

Santisteban

Hang

Smith

2011

Molecular and Cellular Biology

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Nucleosomes containing histone variant H2A.Z (Htz1) serve to poise quiescent genes for activation and transcriptional initiation. However, little is known about their role in transcription elongation. Here we show that dominant mutations in the elongation genes SPT5 and SPT16 suppress the hypersensitivity of htz1⌬ strains to drugs that inhibit elongation, indicating that Htz1 functions at the level of transcription elongation. Direct kinetic measurements of RNA polymerase II (Pol II) movement across the 9.5-kb GAL10p-VPS13 gene revealed that the elongation rate of polymerase is 24% slower in the absence of Htz1. We provide evidence for two nonexclusive mechanisms. First, we observed that both the phospho-Ser2 levels in the elongating isoform of Pol II and the loading of Spt5 and Elongator over the GAL1 open reading frame (ORF) depend on Htz1. Second, in the absence of Htz1, the density of nucleosome occupancy is increased over the GAL10p-VPS13 ORF and the chromatin is refractory to remodeling during active transcription. These results establish a mechanistic role for Htz1 in transcription elongation and suggest that Htz1-containing nucleosomes facilitate Pol II passage by affecting the correct assembly and modification status of Pol II elongation complexes and by favoring efficient nucleosome remodeling over the gene.Transcription by RNA polymerase II (Pol II) takes place on a compositionally and topologically complex chromatin template at multiple steps, including promoter activation, transcription initiation, elongation, and termination. A number of mechanisms facilitate the initiation of gene transcription on chromatin templates. Two of the most prominent of these are the remodeling of nucleosomes by DNA-dependent ATPase complexes and the covalent posttranslational modification of histone proteins (20,90). At a minimum, these pathways are thought to act by establishing a permissive chromatin structure at gene promoters, allowing access of site-specific transcription factors and the subsequent recruitment of polymerase and the general factors (25,69).

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Section: Discussionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Histone Variant H2A.Z and RNA Polymerase II Transcription Elongation

Santisteban

Hang

Smith

2011

Molecular and Cellular Biology

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Characterization and optimization of the LAC4 upstream region for low‐leakage expression in Kluyveromyces marxianus

Liu

Zhou

et al. 2021

Yeast

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Kluyveromyces marxianus is a promising host for the production of heterologous proteins, chemicals, and bioethanol. One superior feature of this species is its capacity to assimilate lactose, which is rendered by the LAC12–LAC4 gene pair encoding a lactose permease and a β‐galactosidase enzyme. Little is known about the regulation of LAC4 in K. marxianus. In this study, we showed the presence of weak glucose repression in the regulation of LAC4 and that might contribute to the leaky expression of LAC4 in the glucose medium. In a mutagenesis screen of 1000‐bp LAC4 upstream region, one mutant region, named H1, drove low‐leakage expression of a URA3 reporter gene in glucose medium. Two mutations inside a polyadenosine stretch (poly(A)) of 5′ UTR were major contributors to the low‐leakage phenotype of H1. H1 directed low‐leakage expression of GFP on a plasmid and that of LAC4 in situ in the glucose medium, which was not due to the reduction of mRNA levels. Meanwhile, H1 did not affect the induction of GFP or LAC4 by lactose. Cre recombinase expressed by H1 caused lower toxicity in the repressive condition and achieved higher yield after induction, compared with that expressed by a wild‐type LAC4 upstream region or a strong INU1 promoter. Our study suggested that poly(A) inside 5′ UTR played a role in regulating the expression of LAC4 in the repressive condition. Meanwhile, H1 provided a base for the development of a strict inducible system for expressing industrial proteins, especially toxic proteins.

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