Structural mechanism of bivalent histone H3K4me3K9me3 recognition by the Spindlin1/C11orf84 complex in rRNA transcription activation

  • Nat Commun. 2021 Feb 11;12(1):949. doi: 10.1038/s41467-021-21236-x.
Yongming Du  1 ,  Yinxia Yan  1 ,  Si Xie  1 ,  Hao Huang  2 ,  Xin Wang  2 ,  Ray Kit Ng  1 ,  Ming-Ming Zhou  3 ,  Chengmin Qian  4
Affiliations
  • 1. School of Biomedical Sciences, The University of Hong Kong, Hong Kong Island, Hong Kong.
  • 2. Department of Biomedical Sciences, The City University of Hong Kong, Kowloon, Hong Kong.
  • 3. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4. School of Biomedical Sciences, The University of Hong Kong, Hong Kong Island, Hong Kong. [email protected].
PMID: 33574238 DOI: 10.1038/s41467-021-21236-x
Abstract

Spindlin1 is a unique multivalent epigenetic reader that facilitates ribosomal RNA transcription. In this study, we provide molecular and structural basis by which Spindlin1 acts in complex with C11orf84 to preferentially recognize non-canonical bivalent MARK of trimethylated lysine 4 and lysine 9 present on the same histone H3 tail (H3K4me3K9me3). We demonstrate that C11orf84 binding stabilizes Spindlin1 and enhances its association with bivalent H3K4me3K9me3 MARK. The functional analysis suggests that Spindlin1/C11orf84 complex can displace HP1 proteins from H3K4me3K9me3-enriched rDNA loci, thereby facilitating the conversion of these poised rDNA repeats from the repressed state to the active conformation, and the consequent recruitment of RNA Polymerase I for rRNA transcription. Our study uncovers a previously unappreciated mechanism of bivalent H3K4me3K9me3 recognition by Spindlin1/C11orf84 complex required for activation of rRNA transcription.