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Acidic domains differentially read histone H3 lysine 4 methylation status and are widely present in chromatin-associated proteins

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An Erratum to this article was published on 12 April 2017

Abstract

Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin (NPM1), pp32, SET/TAF1β, nucleolin (NCL) and upstream binding factor (UBF) are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4me1 and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2. Furthermore, we demonstrate that the acidic domain with sufficient length alone is capable of binding H3K4me2 in vitro and in vivo. NPM1, NCL and UBF require their acidic domains for association with and transcriptional activation of rDNA genes. Interestingly, by defining acidic domain as a sequence with at least 20 acidic residues in 50 continuous amino acids, we identified 655 acidic domain-containing protein coding genes in the human genome and Gene Ontology (GO) analysis showed that many of the acidic domain proteins have chromatin-related functions. Our data suggest that acidic domain is a novel histone binding motif that can differentially read the status of H3K4 methylation and is broadly present in chromatin-associated proteins.

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Acknowledgements

We acknowledge Dr. Jinqiu Zhou for kindly providing H3K4me2 peptide and Dr. Philippe Bouvet for nucleolin antibody. We thank members of Wong’s laboratory for valuable discussion. Meng Wu, Wei Wei, Jiwen Li, Jiemin Wong, and James X. Du conceived and designed the study. Meng Wu, Wei Wei, Q.Z. and Rong Cong performed the experiments. Jiwei Chen and Tieliu Shi carried out bioinformatics analysis. Jiemin Wong and James X. Du wrote the manuscript. All the authors read and approve the final manuscript. This work was supported by the Ministry of Science and Technology of China (2015CB910402) to Jiemin Wong, the National Natural Science Foundation of China (91419303), The Science and Technology Commission of Shanghai Municipality (14XD1401700, 11DZ2260300), the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (2014ZX09507002-002).

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Authors and Affiliations

  1. Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China

    Meng Wu, Wei Wei, Jiwei Chen, Tieliu Shi, Jiwen Li, Jiemin Wong & James X. Du

  2. Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Jiemin Wong

  3. Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS USR 3010, Laboratoire Joliot-Curie, Lyon, 69364, France

    Rong Cong

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  1. Meng Wu
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  2. Wei Wei
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  3. Jiwei Chen
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  6. Jiwen Li
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  8. James X. Du
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Correspondence to Jiemin Wong or James X. Du.

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An erratum to this article is available at http://dx.doi.org/10.1007/s11427-017-9025-9.

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Wu, M., Wei, W., Chen, J. et al. Acidic domains differentially read histone H3 lysine 4 methylation status and are widely present in chromatin-associated proteins. Sci. China Life Sci. 60, 138–151 (2017). https://doi.org/10.1007/s11427-016-0413-3

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