L3MBTL1, a Histone-Methylation-Dependent Chromatin Lock

Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey, 683 Hoes Lane, Piscataway, NJ 08854, USA.
Cell (Impact Factor: 32.24). 07/2007; 129(5):915-28. DOI: 10.1016/j.cell.2007.03.048
Source: PubMed


Distinct histone lysine methylation marks are involved in transcriptional repression linked to the formation and maintenance of facultative heterochromatin, although the underlying mechanisms remain unclear. We demonstrate that the malignant-brain-tumor (MBT) protein L3MBTL1 is in a complex with core histones, histone H1b, HP1gamma, and Rb. The MBT domain is structurally related to protein domains that directly bind methylated histone residues. Consistent with this, we found that the L3MBTL1 MBT domains compact nucleosomal arrays dependent on mono- and dimethylation of histone H4 lysine 20 and of histone H1b lysine 26. The MBT domains bind at least two nucleosomes simultaneously, linking repression of transcription to recognition of different histone marks by L3MBTL1. Consistently, L3MBTL1 was found to negatively regulate the expression of a subset of genes regulated by E2F, a factor that interacts with Rb.

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Available from: Hediye Erdjument-Bromage, Apr 29, 2015
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    • "The targets also can be within one nucleosome, such as in the case of the PRC2 complex , which binds to a nucleosome through multiple contacts, including H3K27me, the H3 tail and H4 tails (Margueron et al., 2009; Murzina et al., 2008). Finally, nucleosomal targets can be spread over multiple nucleosomes, as has been shown for the SIR complex (Martino et al., 2009) and L3MBTL1 (Trojer et al., 2007). Another feature of chromatin structure that has emerged as a key recognition site for the chromatin complex is the linker DNA and the space between adjacent nucleosomes. "
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    Cell Reports 01/2015; 28(2). DOI:10.1016/j.celrep.2014.12.027 · 8.36 Impact Factor
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    • "This article is protected by copyright . All rights reserved . 36 L3MBTL1 is a transcriptional repressor that binds monomethyl H3K4 or dimethylated H4K20 through its three MBT ( malignant brain tumor ) domains to effect the compaction of nucleosomes ( Trojer et al . , 2007 ) . L3MBTL1 interacts with TP53 that is monomethylated at Lys382 by SET8 and is recruited to TP53 target genes to repress TP53 - mediated induction under basal conditions ( Fig . 5 ) . In vitro , L3MBT1 can bind a dimethylated Lys382 peptide with equal affinity ( West et al . , 2010 ) . In response to DNA damage , the levels of SET8 and"
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    • "Importantly, the isolated 3xMBT domain forms no significant contacts with the side chains of amino acids surrounding the methylated residue, providing a structural basis for sequence-independent binding to methyllysine. The specificity of L3MBTL1 for physiologically relevant methylated proteins such as H4 and Rb is thought to be conferred by the 3xMBT binding to methyllysine in combination with nonmethyl-sensitive interactions mediated by regions outside of the 3xMBT domain (Trojer et al., 2007). "
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