The Hda1 histone deacetylase limits divergent non-coding transcription and restricts transcription initiation frequency
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The Hda1 histone deacetylase limits divergent non-coding transcription and restricts transcription initiation frequency. / Gowthaman, Uthra; Ivanov, Maxim; Schwarz, Isabel; Patel, Heta P.; Müller, Niels A.; Garcia-Pichardo, Desire; Lenstra, Tineke L.; Marquardt, Sebastian.
In: EMBO Journal, Vol. 40, No. 23, 108903, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Hda1 histone deacetylase limits divergent non-coding transcription and restricts transcription initiation frequency
AU - Gowthaman, Uthra
AU - Ivanov, Maxim
AU - Schwarz, Isabel
AU - Patel, Heta P.
AU - Müller, Niels A.
AU - Garcia-Pichardo, Desire
AU - Lenstra, Tineke L.
AU - Marquardt, Sebastian
PY - 2021
Y1 - 2021
N2 - Nucleosome-depleted regions (NDRs) at gene promoters support initiation of RNA polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA and a divergent non-coding (DNC) transcript of unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. Using high-throughput reverse genetic screens based on quantitative single-cell fluorescence measurements, we identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC transcription. Nascent transcription profiling showed a genome-wide role of Hda1C in repression of DNC transcription. Live-cell imaging of transcription revealed that mutations in the Hda3 subunit increased the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC transcription regions, supporting DNC transcription repression by histone deacetylation. Our data support the interpretation that DNC transcription results as a consequence of the NDR-based architecture of eukaryotic promoters, but that it is governed by locus-specific repression to maintain genome fidelity.
AB - Nucleosome-depleted regions (NDRs) at gene promoters support initiation of RNA polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA and a divergent non-coding (DNC) transcript of unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. Using high-throughput reverse genetic screens based on quantitative single-cell fluorescence measurements, we identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC transcription. Nascent transcription profiling showed a genome-wide role of Hda1C in repression of DNC transcription. Live-cell imaging of transcription revealed that mutations in the Hda3 subunit increased the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC transcription regions, supporting DNC transcription repression by histone deacetylation. Our data support the interpretation that DNC transcription results as a consequence of the NDR-based architecture of eukaryotic promoters, but that it is governed by locus-specific repression to maintain genome fidelity.
KW - divergent non-coding (DNC) transcription
KW - live-cell imaging
KW - non-coding RNA (ncRNA)
KW - RNA polymerase II transcription
KW - GENE-EXPRESSION
KW - BIDIRECTIONAL PROMOTERS
KW - RNA
KW - REVEALS
KW - DYNAMICS
KW - ACETYLATION
KW - ELONGATION
KW - FIDELITY
KW - GENOME
KW - NOISE
U2 - 10.15252/embj.2021108903
DO - 10.15252/embj.2021108903
M3 - Journal article
C2 - 34661296
VL - 40
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 23
M1 - 108903
ER -
ID: 283774396