Recognition of acetylated histone by Yaf9 regulates metabolic cycling of transcription initiation and chromatin regulatory factors

How transcription programs rapidly adjust to changing metabolic and cellular cues remains poorly defined. Here, we reveal a function for the Yaf9 component of the SWR1-C and NuA4 chromatin regulatory complexes in maintaining timely transcription of metabolic genes across the yeast metabolic cycle (YMC). By reading histone acetylation during the oxidative and respiratory phase of the YMC, Yaf9 recruits SWR1-C and NuA4 complexes to deposit H2A.Z and acetylate H4, respectively. Increased H2A.Z and H4 acetylation during the oxidative phase promotes transcriptional initiation and chromatin machinery occupancy and is associated with reduced RNA polymerase II levels at genes—a pattern reversed during transition from oxidative to reductive metabolism. Prevention of Yaf9-H3 acetyl reading disrupted this pattern of transcriptional and chromatin regulator recruitment and impaired the timely transcription of metabolic genes. Together, these findings reveal that Yaf9 contributes to a dynamic chromatin and transcription initiation factor signature that is necessary for the proper regulation of metabolic gene transcription during the YMC. They also suggest that unique regulatory mechanisms of transcription exist at distinct metabolic states.

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DOT1L complex regulates transcriptional initiation in human erythroleukemic cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2106148118 ◽

2021 ◽

Vol 118 (27) ◽

pp. e2106148118

Author(s):

Aiwei Wu ◽

Junhong Zhi ◽

Tian Tian ◽

Ali Cihan ◽

Murat A. Cevher ◽

...

Keyword(s):

Rna Polymerase Ii ◽

Transcription Initiation ◽

Target Genes ◽

Initiation Factor ◽

Transcriptional Elongation ◽

Saga Complex ◽

Transcriptional Initiation ◽

Pol Ii ◽

Transcription Initiation Factor ◽

Erythroleukemic Cells

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes. More importantly, DOT1L and ENL depletions concomitantly reduce TBP and Pol II occupancies on a significant fraction of direct (DOT1L-bound) target genes, indicating a role for the DOT1L complex in transcription initiation. Mechanistically, proteomic and biochemical studies suggest that the DOT1L complex may regulate transcriptional initiation by facilitating the recruitment or stabilization of transcription factor IID, likely in a monoubiquitinated H2B (H2Bub1)-enhanced manner. Additional studies show that DOT1L enhances H2Bub1 levels by limiting recruitment of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. These results advance our understanding of roles of the DOT1L complex in transcriptional regulation and have important implications for MLLr leukemias.

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Structure and associated DNA-helicase activity of a general transcription initiation factor that binds to RNA polymerase II

Nature ◽

10.1038/341410a0 ◽

1989 ◽

Vol 341 (6241) ◽

pp. 410-414 ◽

Cited By ~ 109

Author(s):

Mary Sopta ◽

Zachary F. Burton ◽

Jack Greenblatt

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcription Initiation ◽

Dna Helicase ◽

Initiation Factor ◽

Helicase Activity ◽

Transcription Initiation Factor

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The C-terminal domain of the largest subunit of RNA polymerase II and transcription initiation

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5750-5753.1989 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5750-5753

Author(s):

M Moyle ◽

J S Lee ◽

W F Anderson ◽

C J Ingles

Keyword(s):

Monoclonal Antibodies ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcription Initiation ◽

Initiation Factor ◽

Transcription Initiation Factor ◽

Evolutionarily Conserved ◽

Repeat Domain ◽

Initiation Of Transcription

Monoclonal antibodies specific for the evolutionarily conserved C-terminal heptapeptide repeat domain of the largest subunit of RNA polymerase II inhibited the initiation of transcription from mammalian promoters in vitro. Since these antibodies did not inhibit elongation and randomly initiated transcription, the heptapeptide repeats may function by binding class II transcription initiation factor(s).

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The C-terminal domain of the largest subunit of RNA polymerase II and transcription initiation.

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5750 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5750-5753 ◽

Cited By ~ 14

Author(s):

M Moyle ◽

J S Lee ◽

W F Anderson ◽

C J Ingles

Keyword(s):

Monoclonal Antibodies ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcription Initiation ◽

Initiation Factor ◽

Transcription Initiation Factor ◽

Evolutionarily Conserved ◽

Repeat Domain ◽

Initiation Of Transcription

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Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2

Cells ◽

10.3390/cells10123510 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3510

Author(s):

Ray Ishida ◽

Jamie Cole ◽

Joaquin Lopez-Orozco ◽

Nawell Fayad ◽

Alberto Felix-Lopez ◽

...

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcription Initiation ◽

Initiation Factor ◽

Induction Phase ◽

Type I ◽

Structural Protein ◽

Host Proteins ◽

Transcription Initiation Factor ◽

Mayaro Virus

Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses.

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The T Body, a New Cytoplasmic RNA Granule in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.00684-08 ◽

2008 ◽

Vol 28 (19) ◽

pp. 6022-6032 ◽

Cited By ~ 27

Author(s):

Francisco Malagon ◽

Torben Heick Jensen

Keyword(s):

Saccharomyces Cerevisiae ◽

Rna Polymerase Ii ◽

Transcription Initiation ◽

Initiation Factor ◽

Confined Space ◽

Large Share ◽

Cytoplasmic Rna ◽

Transcription Initiation Factor ◽

Genes Encoding ◽

Mrna Fate

ABSTRACT A large share of mRNA processing and packaging events occurs cotranscriptionally. To explore the hypothesis that transcription defects may affect mRNA fate, we analyzed poly(A)+ RNA distribution in Saccharomyces cerevisiae strains harboring mutations in Rpb1p, the largest subunit of RNA polymerase II. In certain rpb1 mutants, a poly(A)+ RNA granule, distinct from any known structure, strongly accumulated in a confined space of the cytoplasm. RNA and protein expressed from Ty1 retrovirus-like elements colocalized with this new granule, which we have consequently named the T body. A visual screen revealed that the deletion of most genes with proposed functions in Ty1 biology unexpectedly does not alter T-body levels. In contrast, the deletion of genes encoding the Mediator transcription initiation factor subunits Srb2p and Srb5p as well as the Ty1 transcriptional regulator Spt21p greatly enhances T-body formation. Our data disclose a new cellular body putatively involved in the assembly of Ty1 particles and suggest that the cytoplasmic fate of mRNA can be affected by transcription initiation events.

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