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

• Published in: Nature communications Vol. 12; no. 1; p. 949
• Main Authors: Du, Yongming, Yan, Yinxia, Xie, Si, Huang, Hao, Wang, Xin, Ng, Ray Kit, Zhou, Ming-Ming, Qian, Chengmin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.02.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Cell Cycle Proteins - metabolism; Cell Proliferation; Conformation; DNA, Ribosomal - genetics; DNA, Ribosomal - metabolism; DNA-directed RNA polymerase; Epigenetics; Functional analysis; Genes, rRNA; HEK293 Cells; Histone H3; Histones; Histones - metabolism; Humans; Lysine; Microtubule-Associated Proteins - metabolism; Phosphoproteins - metabolism; Recognition; RNA polymerase; RNA Polymerase I; RNA, Ribosomal - metabolism; rRNA; Transcription activation; Transcription, Genetic; Transcriptional Activation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21236-x

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.