Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation

By Till Bartke, M. Vermeulen, Blerta Xhemalçe, S. Robson, Matthias Mann, Tony Kouzarides. Cell, 2010

625 citations recorded by the source corpus.

Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify “cross-talk” between these two distinct classes of modification. Our analysis reveals proteins whose binding to nucleosomes is regulated by methylation of CpGs, H3K4, H3K9, and H3K27 or a combination thereof. We identify the Origin Recognition Complex (ORC), including LRWD1 as a subunit, to be a methylation-sensitive nucleosome interactor which is recruited cooperatively by DNA and histone methylation. Other interactors, such as the lysine demethylase Fbxl11/KDM2A, recognise nucleosomes methylated on histones but their recruitment is disrupted by DNA methylation. These data establish SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications and provide a modification binding “profile” for proteins regulated by DNA and histone methylation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/20ec22a512a0132702bc841fe7452fbbd388b206

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Citations in the corpus

NF-κB, the first quarter-century: remarkable progress and outstanding questions. (2012, neutral): “approach (Bartke et al. 2010).”
Understanding the language of Lys36 methylation at histone H3 (2012, background): “Originally identified in NSD2, PWWP domains also bind H3K36me3 to act as reader protein”
Interpreting thelanguage of histone and DNA modifications (2014, methodology): “PHD fingers shown to read H3K4me3 [116,117,163].”
The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGFβ and Hippo pathways (2022, background): “Early mass spectrometry analysis of proteins associated with nucleosomes whose histones presented specific posttranslational modifications demonstrated that PHF14 and HMG20A were among the few proteins excluded from nucleosomes containing the H3K4me3 modification, but associated with H3K4-unmodified”
Cancer epigenetics: from mechanism to therapy. (2012, methodology): “The concept of multivalent engagement by chromatin-binding modules has recently been explored by using either modified histone peptides (Vermeulen et al., 2010) or in-vitro-assembled and -modified nucleosomes (Bartke et al., 2010; Ruthenburg et al., 2011).”
A decade of exploring the cancer epigenome — biological and translational implications (2011, background): “These possibilities are consistent with recent data that methylated DNA in a nucleosomal context actually repels components of PcG”
Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. (2013, positive): “Interestingly, OCR, or Spindlin-1, is a protein that is known to bind trimethylated H3 lysine 4 (H3K4me3) (Bartke et al., 2010).”
A double take on bivalent promoters. (2013, background): “4B; Bartke et al. 2010).”
DNA methylation presents distinct binding sites for human transcription factors (2013, background): “…of 16 Research article only MeCP2, MBD1, MBD2, and a few zinc finger proteins have been identified as bona fide methylated DNA-binding proteins (Lewis et al., 1992; Meehan et al., 1989; Filion et al., 2006; Bartke et al., 2010; Bartels et al., 2011; Quenneville et al., 2011; Spruijt et al., 2013).”
Pioneer transcription factors: establishing competence for gene expression. (2011, background): “Recent studies indicate that specific complexes of factors directly bind to specific combinations of modified histones (Bartke et al. 2010) apparently sensitive to specific histone codes (Turner 1993; Strahl and Allis 2000; Li et al.”
Epigenetic Determinants of Cancer. (2016, background): “Experimental data corroborating this show that methylated DNA, when in a nucleosomal context, is resistant to the presence of PcG complexes and, hence, the imposition of the silencing H3K27me marks (Schlesinger et al. 2007; Widschwendter et al. 2007; Gal-Yam et al. 2008; Bartke et al. 2010).”