Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications

Musselman, Catherine A.; Mansfield, Robyn E.; Garske, Adam L.; Davrazou, Foteini; Kwan, Ann H.; Oliver, Samuel S.; O’Leary, Heather; Denu, John M.; Mackay, Joel P.; Kutateladze, Tatiana G.

doi:10.1042/bj20090870

Cited by 107 publications

(101 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Emission spectra were recorded from 305 to 405 nm with a 0.5 nm step size and a 1 s integration time, averaged over 3 scans. The K d s were determined as described (Musselman et al, 2009; Musselman et al, 2012b). The K d values were averaged over three separate experiments, with error calculated as the standard deviation between runs.…”

Section: Methodsmentioning

confidence: 99%

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1

et al. 2015

Self Cite

View full text Add to dashboard Cite

SUMMARY p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 co-factor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.

show abstract

Section: Methodsmentioning

confidence: 99%

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…As the PHD domains in DPF3 and NURF301 proteins have been reported to bind to acetylated and methylated histones, respectively (20,36), the REQ PHDs may exert a transactivation function by linking the large complex composed of SWI/SNF, REQ, and RelB/p52 to nucleosomes that contain specifically modified histone tails. Importantly, the core components of the SWI/SNF complexes have no PHD finger domains, whereas many other chromatin remodeling complexes, for example ISWI (37,38) and Mi-2␤ (36,39), do contain subunits with PHD domains. In our current experiments, REQ-dependent luciferase reporter gene expression was detectable only when the gene was stably integrated but transiently introduced.…”

Section: Discussionmentioning

confidence: 99%

Requiem Protein Links RelB/p52 and the Brm-type SWI/SNF Complex in a Noncanonical NF-κB Pathway

Tando

Ishizaka

Watanabe

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The SWI/SNF chromatin remodeling complex plays pivotal roles in mammalian transcriptional regulation. In this study, we identify the human requiem protein (REQ/DPF2) as an adaptor molecule that links the NF-B and SWI/SNF chromatin remodeling factor. Through in vitro binding experiments, REQ was found to bind to several SWI/SNF complex subunits and also to the p52 NF-B subunit through its nuclear localization signal containing the N-terminal region. REQ, together with Brm, a catalytic subunit of the SWI/SNF complex, enhances the NF-Bdependent transcriptional activation that principally involves the RelB/p52 dimer. Both REQ and Brm were further found to be required for the induction of the endogenous BLC (CXCL13) gene in response to lymphotoxin stimulation, an inducer of the noncanonical NF-B pathway. Upon lymphotoxin treatment, REQ and Brm form a larger complex with RelB/p52 and are recruited to the BLC promoter in a ligand-dependent manner. Moreover, a REQ knockdown efficiently suppresses anchorageindependent growth in several cell lines in which the noncanonical NF-B pathway was constitutively activated. From these results, we conclude that REQ functions as an efficient adaptor protein between the SWI/SNF complex and RelB/p52 and plays important roles in noncanonical NF-B transcriptional activation and its associated oncogenic activity.The SWI/SNF (switch/sucrose-nonfermentable) chromatin remodeling complex has important functional roles in the epigenetic regulation of many organisms and regulates a wide variety of genes (1, 2). In mammals, this complex is an assembly of about nine polypeptides and contains a single molecule of either Brm or BRG1 but not both (3). These two proteins are the catalytic subunits that together with noncatalytic subunits, such as BAF170, BAF155, Ini1, BAF60a, and ␤-actin, drive the remodeling of nucleosomes via their ATP-dependent helicase activity (4). Evidence has now accumulated that the Brm-type and BRG1-type SWI/SNF complexes regulate a set of target promoters that do not fully overlap. Indeed, Brm and BRG1 show clear differences in their biological activities. For example, Brm-type, but not BRG1-type, SWI/SNF complexes are essential for the maintenance of gene expression driven by the long terminal repeats of murine leukemia virus (5, 6) and human immunodeficiency virus (7). Moreover, in gastrointestinal cells, Brm but not BRG1 can transactivate Cdx2-dependent villin expression, even though both proteins can interact with Cdx2 (8). Overall, the SWI/SNF complexes interact with various proteins, including transcriptional regulators, through the many specific and varied associations with their subunits. We previously demonstrated that among all of the dimers formed between Fos and Jun family proteins, which compose the representative transcription factor AP-1, the c-Fos/c-Jun heterodimer most efficiently recruits SWI/SNF complexes to AP-1-binding sites through its specific binding activity to the BAF60a SWI/SNF subunit (9).Like AP-1, the NF-B 3 is an important transcription facto...

show abstract

“…tandem PHD (plant homeodomain) fingers (Figure 1b). The structurally and functionally similar PHD fingers recognize the H3K9me0 (unmodified histone H3) or H3K9me3 tails [9,10]. Binding to H3K9me0 and H3K9me3 has been shown to play a critical role in the repressive transcriptional and chromatin remodelling functions of CHD4 [11].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of histone binding by supramolecular hosts

Allen

Daze

Shimbo

et al. 2014

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

The tandem PHD (plant homeodomain) fingers of the CHD4 (chromodomain helicase DNA-binding protein 4) ATPase are epigenetic readers that bind either unmodified histone H3 tails or H3K9me3 (histone H3 trimethylated at Lys9). This dual function is necessary for the transcriptional and chromatin remodelling activities of the NuRD (nucleosome remodelling and deacetylase) complex. In the present paper, we show that calixarene-based supramolecular hosts disrupt binding of the CHD4 PHD2 finger to H3K9me3, but do not affect the interaction of this protein with the H3K9me0 (unmodified histone H3) tail. A similar inhibitory effect, observed for the association of chromodomain of HP1γ (heterochromatin protein 1γ) with H3K9me3, points to a general mechanism of methyl-lysine caging by calixarenes and suggests a high potential for these compounds in biochemical applications. Immunofluorescence analysis reveals that the supramolecular agents induce changes in chromatin organization that are consistent with their binding to and disruption of H3K9me3 sites in living cells. The results of the present study suggest that the aromatic macrocyclic hosts can be used as a powerful new tool for characterizing methylation-driven epigenetic mechanisms.

show abstract

Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications

Cited by 107 publications

References 38 publications

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1

Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1

Requiem Protein Links RelB/p52 and the Brm-type SWI/SNF Complex in a Noncanonical NF-κB Pathway

Inhibition of histone binding by supramolecular hosts

Contact Info

Product

Resources

About