Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1.
Yang N, Wang W, Wang Y, Wang M, Zhao Q, Rao Z, Zhu B, Xu RM
Oct. 17, 2012 ----Dr. Bing Zhu's lab, in collaboration with Dr. Rui-ming Xu's lab at the Institute of Biophysics, Chinese Academy of Sciences, uncovered the mechanism of nucleolar protein Spindlin1 regulating rRNA gene transcription. The finding was published as a research article entitled "Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1" in PNAS on Oct. 17, 2012.
In 2011, in collaboration with Dr. Rui-ming Xu's lab at the Institute of Biophysics, Chinese Academy of Sciences, Dr. Bing Zhu's lab published a research article entitled "Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes" in EMBO Reports, which reported a nucleolar protein spindlin1 that specifically recognizes histone H3K4me3 and regulates rRNA gene expression.
In the current report, Dr. Rui-ming Xu's lab resolved the crystal structure of Spindlin1 in complex with H3K4me3 peptide and discovered a novel binding mode of H3K4me3 recognition. Dr. Bing Zhu's lab confirmed the roles of the critical Spindlin1 residues in rRNA gene transcription regulation.
Drs. Na Yang (Rui-Ming Xu lab), Weixiang Wang (Bing Zhu lab) and Yan Wang (Rui-ming Xu lab) are the equal contributing first authors of this paper. Drs. Rui-Ming Xu, Bing Zhu and Na Yang are the corresponding authors. Other authors include Dr. Qiang Zhao at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Dr. Zihe Rao at the Institute of Biophysics, Chinese Academy of Sciences. This study was supported by grants from the Chinese Ministry of Science and Technology, the Chinese Nature Science Foundation and the International Early Career Scientist Program of the Howard Hughes Medical Institute.
Recognition of methylated histone tail lysine residues by tudor domains plays important roles in epigenetic control of gene expression and DNA damage response. Previous studies revealed the binding of methyllysine in a cage of aromatic residues, but the molecular mechanism by which the sequence specificity for surrounding histone tail residues is achieved remains poorly understood. In the crystal structure of a trimethylated histone H3 lysine 4 (H3K4) peptide bound to the tudor-like domains of Spindlin1 presented here, an atypical mode of methyllysine recognition by an aromatic pocket of Spindlin1 is observed. Furthermore, the histone sequence is recognized in a distinct manner involving the amino terminus and a pair of arginine residues of histone H3, and disruption of the binding impaired stimulation of pre-RNA expression by Spindlin1. Our analysis demonstrates considerable diversities of methyllysine recognition and sequence-specific binding of histone tails by tudor domains, and the revelation furthers the understanding of tudor domain proteins in deciphering epigenetic marks on histone tails.