Related Experiment Video
Updated: May 28, 2026
Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9
Jing Li1, Zhihong Li, Jianbin Ruan
1Key Laboratory of Structural Biology, Chinese Academy of Sciences, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Background:
M-phase phosphoprotein 8 (MPP8) was initially identified to be a component of the RanBPM-containing large protein complex, and has recently been shown to bind to methylated H3K9 both in vivo and in vitro. MPP8 binding to methylated H3K9 is suggested to recruit the H3K9 methyltransferases GLP and ESET, and DNA methyltransferase 3A to the promoter of the E-cadherin gene, mediating the E-cadherin gene silencing and promote tumor cell motility and invasion. MPP8 contains a chromodomain in its N-terminus, which is used to bind the methylated H3K9.
Methodology/Principal Findings:
Here, we reported the crystal structures of human MPP8 chromodomain alone and in complex with the trimethylated histone H3K9 peptide (residue 1-15). The complex structure unveils that the human MPP8 chromodomain binds methylated H3K9 through a conserved recognition mechanism, which was also observed in Drosophila HP1, a chromodomain containing protein that binds to methylated H3K9 as well. The structure also reveals that the human MPP8 chromodomain forms homodimer, which is mediated via an unexpected domain swapping interaction through two β strands from the two protomer subunits.
Conclusions/Significance:
Our findings reveal the molecular mechanism of selective binding of human MPP8 chromodomain to methylated histone H3K9. The observation of human MPP8 chromodomain in both solution and crystal lattice may provide clues to study MPP8-mediated gene regulation furthermore.
Insights
M-phase phosphoprotein 8 (MPP8) binds to methylated H3K9 via its chromodomain. This interaction, revealed by crystal structures, involves a conserved mechanism and MPP8 homodimerization, offering insights into gene regulation.
Area of Science:
- Epigenetics and Molecular Biology
- Structural Biology
- Cancer Research
Background:
- M-phase phosphoprotein 8 (MPP8) binds to methylated H3K9, a mark associated with gene silencing.
- MPP8's interaction with H3K9 is implicated in recruiting epigenetic modifiers and promoting tumor cell invasion.
- The N-terminal chromodomain of MPP8 is responsible for binding to methylated H3K9.
Purpose of the Study:
- To elucidate the molecular mechanism of human MPP8 chromodomain binding to methylated histone H3K9.
- To determine the crystal structures of the human MPP8 chromodomain alone and in complex with a methylated H3K9 peptide.
Main Methods:
- X-ray crystallography was used to determine the structures of the human MPP8 chromodomain.
- Co-crystallization of the MPP8 chromodomain with a trimethylated histone H3K9 peptide.
Main Results:
- The crystal structure of the human MPP8 chromodomain alone and in complex with methylated H3K9 peptide was determined.
- MPP8 chromodomain binds methylated H3K9 via a conserved mechanism, similar to Drosophila HP1.
- Human MPP8 chromodomain forms homodimers through an unexpected domain swapping interaction.
Conclusions:
- The study reveals the molecular basis for selective binding of the human MPP8 chromodomain to methylated histone H3K9.
- The observed homodimerization of MPP8 may play a role in its function in gene regulation.
- These findings provide a foundation for further investigation into MPP8-mediated gene regulation.
Related Concept Videos
02:32Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:38Heterochromatin
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
01:12The Nucleosome Core Particle
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
02:10The Nucleosome Core Particle
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:25Spreading of Chromatin Modifications
Writers
The writer is an enzyme that can...
02:30Histone Variants at the Centromere