Structural study of DNMT1-histone interaction

LINHUI LI, University of California, Riverside
JIKUI SONG, University of California, Riverside

Abstract

DNA methyltransferase 1 (DNMT1) mediates maintenance of DNA methylation patterns in genome, thus, results in epigenetic inheritance during cell division. Structurally, DNMT1 is composed of a replication foci targeting sequence (RFTS), a DNA-binding CXXC domain, a pairs of Bromo-adjacent homology (BAH) domains, and a C-terminal methyltransferase domain. Previous structural studies of the DNMT1-DNA complex revealed that the CXXC domain and the methyltransferase domain are responsible for interactions with unmethylated and hemimethylated CpG dinucleotides, respectively. However, whether and how DNMT1-mediated methylation cross talks with other epigenetic pathway remain unresolved. Our recent study identified that the BAH domain of origin of replication complex subunit 1 (ORC1) recognizes histone H4 dimethylated at lysine 20 (H4K20me2); such recognition is presumably important for replication-coupled DNA methylation. The protein crystals for DNMT1 BAH domain with H4K20me2 were generated after extensive screening. Further experiments are underway to determine the interaction between the BAH domain and H4K20me2. Our investigation on the molecular interaction between the DNMT1 BAH domain and H4K20me2 through structural study promises to provide critical insights into the functional regulation of DNMT1.

 
Nov 12th, 1:00 PM Nov 12th, 2:00 PM

Structural study of DNMT1-histone interaction

HUB 302-38

DNA methyltransferase 1 (DNMT1) mediates maintenance of DNA methylation patterns in genome, thus, results in epigenetic inheritance during cell division. Structurally, DNMT1 is composed of a replication foci targeting sequence (RFTS), a DNA-binding CXXC domain, a pairs of Bromo-adjacent homology (BAH) domains, and a C-terminal methyltransferase domain. Previous structural studies of the DNMT1-DNA complex revealed that the CXXC domain and the methyltransferase domain are responsible for interactions with unmethylated and hemimethylated CpG dinucleotides, respectively. However, whether and how DNMT1-mediated methylation cross talks with other epigenetic pathway remain unresolved. Our recent study identified that the BAH domain of origin of replication complex subunit 1 (ORC1) recognizes histone H4 dimethylated at lysine 20 (H4K20me2); such recognition is presumably important for replication-coupled DNA methylation. The protein crystals for DNMT1 BAH domain with H4K20me2 were generated after extensive screening. Further experiments are underway to determine the interaction between the BAH domain and H4K20me2. Our investigation on the molecular interaction between the DNMT1 BAH domain and H4K20me2 through structural study promises to provide critical insights into the functional regulation of DNMT1.