1. Academic Validation
  2. A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes

A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes

  • bioRxiv. 2024 Dec 6:2024.12.06.627179. doi: 10.1101/2024.12.06.627179.
Sarah A Tripplehorn 1 Margaret K Shirra 1 Santana M Lardo 1 Hannah G Marvil 1 Sarah J Hainer 1 2 Karen M Arndt 1
Affiliations

Affiliations

  • 1 Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA USA.
  • 2 UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA USA.
Abstract

The nucleosome remodeler Chd1 is required for the re-establishment of nucleosome positioning in the wake of transcription elongation by RNA Polymerase II. Previously, we found that Chd1 occupancy on gene bodies depends on the Rtf1 subunit of the Paf1 complex in yeast. Here, we identify an N-terminal region of Rtf1 and the CHCT domain of Chd1 as sufficient for their interaction and demonstrate that this interaction is direct. Mutations that disrupt the Rtf1-Chd1 interaction result in an accumulation of Chd1 at the 5' ends of Chd1-occupied genes, increased cryptic transcription, altered nucleosome positioning, and concordant shifts in histone modification profiles. We show that a homologous region within mouse RTF1 interacts with the CHCT domains of mouse CHD1 and CHD2. This work supports a conserved mechanism for coupling Chd1 family proteins to the transcription elongation complex and identifies a cellular function for a domain within Chd1 about which little is known.

Keywords

Chd1; Paf1 complex; Rtf1; chromatin; nucleosome remodeling; transcription elongation.

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