4.8 Article

The Arabidopsis DREAM complex antagonizes WDR5A to modulate histone H3K4me2/3 deposition for a subset of genome repression

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2206075119

Keywords

DREAM complex; transcriptional repression; H3K4 methylation

Funding

  1. National Natural Science Foundation of China [31621001, 31871221, 31970259]
  2. National Key Research and Development Program of China [2016YFA0500800]
  3. Peking-Tsinghua Center for Life Sciences

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In this study, a plant-specific component of the DREAM complex called BTE1 was identified. It was found that the DREAM complex containing BTE1 acts against the COMPASS-like complex to repress transcription and occupancy of H3K4me3 at target genes. BTE1 was shown to interact with WDR5A, inhibiting its chromatin binding and transcription elongation on DREAM target genes.
The master transcriptional repressor DREAM (dimerization partner, RB-like, E2F and multivulval class B) complex regulates the cell cycle in eukaryotes, but much remains unknown about how it transmits repressive signals on chromatin to the primary transcriptional machinery (e.g., RNA polymerase II [Pol II]). Through a forward genetic screen, we identified BTE1 (barrier of transcription elongation 1), a plant-specific component of the DREAM complex. The subsequent characterization demonstrated that DREAM complex containing BTE1 antagonizes the activity of Complex Proteins Associated with Set1 (COMPASS)-like complex to repress H3K4me3 occupancy and inhibits Pol II elongation at DREAM target genes. We showed that BTE1 is recruited to chromatin at the promoter-proximal regions of target genes by E2F transcription factors. DREAM target genes exhibit characteristic enrichment of H2A.Z and H3K4me2 modification on chromatin. We further showed that BTE1 directly interacts with WDR5A, a core component of COMPASS-like complex, repressing WDR5A chromatin binding and the elongation of transcription on DREAM target genes. H3K4me3 is known to correlate with the Pol II transcription activation and promotes efficient elongation. Thus, our study illustrates a transcriptional repression mechanism by which the DREAM complex dampens H3K4me3 deposition at a set of genes through its interaction with WDR5A.

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