| Institution: | 1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2. CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China;3. Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China;4. Department of Chemistry & Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada;5. University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China;1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel;2. Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel;3. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel;1. Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada;2. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4M1, Canada;1. IISc Mathematics Initiative, Indian Institute of Science, Bangalore 560012, India;2. NMR Research Centre, Indian Institute of Science, Bangalore 560012, India;3. Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India;1. Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China;2. Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China;3. University of Chinese Academy of Sciences, Beijing, China;4. Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China |
| Abstract: | Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin. |
