Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex

Download

10.1016:j.celrep.2020.03.003.pdf

Date

2020-3

Author

Zhang, Heng
Devoucoux, Maëva
Song, Xiaosheng
Li, Li
Ayaz, Gamze
Cheng, Harry
Tempel, Wolfram
Dong, Cheng
Loppnau, Peter
Côté, Jacques
Min, Jinrong

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

72
views

58
downloads

MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we present the crystal structure of the MBTD1-EPC1 complex, revealing a hydrophobic C-terminal fragment of EPC1 engaging the MBT repeats of MBTD1 in a site distinct from the H4K20me binding site. Different cellular assays validate the physiological significance of the key residues involved in the MBTD1-EPC1 interaction. Our study provides a structural framework for understanding the mechanism by which MBTD1 recruits the NuA4/TIP60 acetyltransferase complex to influence transcription and DNA repair pathway choice.

Subject Keywords

General Biochemistry, Genetics and Molecular Biology

URI

https://hdl.handle.net/11511/51551

Journal

Cell Reports

DOI

https://doi.org/10.1016/j.celrep.2020.03.003

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides. Klinman, DM; Zeuner, R; Yamada, H; Gürsel, Mayda; Currie, D; Gursel, I (Wiley, 2003-12-01) Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work exp...
Functional characterization of microrna-125b expression in MCF7 breast cancer cell line Tuna, Serkan; Erson Bensan, Ayşe Elif; Department of Biology (2010) microRNA dependent gene expression regulation has roles in diverse processes such as differentiation, proliferation and apoptosis. Therefore, deregulated miRNA expression has functional importance for various diseases, including cancer. miR-125b is among the commonly downregulated miRNAs in breast cancer cells . Therefore we aimed to characterize the effects of miR-125b expression in MCF7 breast cancer cell line (BCCL) to better understand its roles in tumorigenesis. Here, we investigated mir-125 family mem...
Investigating the malleability of RNA aptamers İlgü, Müslüm; Lamm, Monica H.; Nilsen-Hamilton, Marit (Elsevier BV, 2013-09-15) Aptamers are short, single-stranded nucleic acids with structures that frequently change upon ligand binding and are sensitive to the ionic environment. To achieve facile application of aptamers in controlling cellular activities, a better understanding is needed of aptamer ligand binding parameters, structures, intramolecular mobilities and how these structures adapt to different ionic environments with consequent effects on their ligand binding characteristics. Here we discuss the integration of biochemic...
Molecular dynamics simulations and coupled nucleotide substitution experiments indicate the nature of A center dot A base pairing and a putative structure of the coralyne-induced homo-adenine duplex Joung, In Suk; Persil Çetinkol, Özgül; HUD, Nicholas V.; Cheatham, Thomas E. (Oxford University Press (OUP), 2009-12-01) Coralyne is an alkaloid drug that binds homo-adenine DNA (and RNA) oligonucleotides more tightly than it does Watson-Crick DNA. Hud's laboratory has shown that poly(dA) in the presence of coralyne forms an anti-parallel duplex, however attempts to determine the structure by NMR spectroscopy and X-ray crystallography have been unsuccessful. Assuming adenine-adenine hydrogen bonding between the two poly(dA) strands, we constructed 40 hypothetical homo-(dA) anti-parallel duplexes and docked coralyne into the s...
Structural properties of an engineered outer membrane protein G mutant, OmpG-16SL, investigated with infrared spectroscopy Yilmaz, Irem; Yildiz, Ozkan; KORKMAZ ÖZKAN, FİLİZ (Informa UK Limited, 2019-05-31) The structural and functional differences between wild type (WT) outer membrane protein G and its two mutants are investigated with Fourier transform infrared spectroscopy. Both mutants have a long extension to the primary sequence to increase the number of beta-strands from 14 (wild type) to 16 in an attempt to enlarge the pore diameter. The comparison among proteins is made in terms of pH-dependent conformational changes and thermal stability. Results show that all proteins respond to pH change but at dif...

Citation Formats

H. Zhang et al., “Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex,” Cell Reports, pp. 3996–4002, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/51551.