scholarly journals Inhibition of histone binding by supramolecular hosts

2014 ◽  
Vol 459 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Hillary F. Allen ◽  
Kevin D. Daze ◽  
Takashi Shimbo ◽  
Anne Lai ◽  
Catherine A. Musselman ◽  
...  
Keyword(s):  
Histone Tail ◽  
Histone Binding ◽  
Phd Finger

We report a new set of calixarene-based host compounds and show their applicability in characterizing functions of methyllysine-recognizing epigenetic readers. Calixarenes disrupt the association of the PHD finger of CHD4 with a trimethylated, but not an unmodified, histone tail.

scholarly journals The Yng1p Plant Homeodomain Finger Is a Methyl-Histone Binding Module That Recognizes Lysine 4-Methylated Histone H3

2006 ◽  
Vol 26 (21) ◽  
pp. 7871-7879 ◽  
Author(s):  
David G. E. Martin ◽  
Kristin Baetz ◽  
Xiaobing Shi ◽  
Kay L. Walter ◽  
Vicki E. MacDonald ◽  
...  
Keyword(s):  
Histone H3 ◽  
General Role ◽  
Histone Binding ◽  
Phd Finger ◽  
Amino Terminal ◽  
Plant Homeodomain Finger ◽  
Plant Homeodomain ◽  
Insight Into

ABSTRACT The ING (inhibitor of growth) protein family includes a group of homologous nuclear proteins that share a highly conserved plant homeodomain (PHD) finger domain at their carboxyl termini. Members of this family are found in multiprotein complexes that posttranslationally modify histones, suggesting that these proteins serve a general role in permitting various enzymatic activities to interact with nucleosomes. There are three members of the ING family in Saccharomyces cerevisiae: Yng1p, Yng2p, and Pho23p. Yng1p is a component of the NuA3 histone acetyltransferase complex and is required for the interaction of NuA3 with chromatin. To gain insight into the function of the ING proteins, we made use of a genetic strategy to identify genes required for the binding of Yng1p to histones. Using the toxicity of YNG1 overexpression as a tool, we showed that Yng1p interacts with the amino-terminal tail of histone H3 and that this interaction can be disrupted by loss of lysine 4 methylation within this tail. Additionally, we mapped the region of Yng1p required for overexpression of toxicity to the PHD finger, showed that this region capable of binding lysine 4-methylated histone H3 in vitro, and demonstrated that mutations of the PHD finger that abolish binding in vitro are no longer toxic in vivo. These results identify a novel function for the Yng1p PHD finger in promoting stabilization of the NuA3 complex at chromatin through recognition of histone H3 lysine 4 methylation.

scholarly journals The PHD finger of Spp1 mediates histone modification cross-talk

2019 ◽  
Vol 476 (16) ◽  
pp. 2351-2354
Author(s):  
Catherine A. Musselman ◽  
Tatiana G. Kutateladze
Keyword(s):  
Histone Modification ◽  
Cross Talk ◽  
Histone Tail ◽  
Post Translational Modifications ◽  
Phd Finger ◽  
Saccharomyces Pombe

Abstract Binding of the Spp1 PHD finger to histone H3K4me3 is sensitive to adjacent post-translational modifications in the histone tail. This commentary discusses the findings of He and colleagues [Biochem. J.476, 1957–1973] which show that the PHD finger binds to H3K4me3 in a selective manner which is conserved in the Saccharomyces pombe and mammalian orthologues of Spp1.

Screening for Inhibitors of Low-Affinity Epigenetic Peptide-Protein Interactions: An AlphaScreen™-Based Assay for Antagonists of Methyl-Lysine Binding Proteins

2009 ◽  
Vol 15 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Tim J. Wigle ◽  
J. Martin Herold ◽  
Guillermo A. Senisterra ◽  
Masoud Vedadi ◽  
Dmitri B. Kireev ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Throughput Screening ◽  
Binding Proteins ◽  
Binding Constants ◽  
Cellular Reprogramming ◽  
Histone Tail ◽  
Target Class ◽  
Screening Assay ◽  
Histone Binding ◽  
High Throughput Screening Assay

The histone code comprises many posttranslational modifications that occur mainly in histone tail peptides. The identity and location of these marks are read by a variety of histone-binding proteins that are emerging as important regulators of cellular differentiation and development and are increasingly being implicated in numerous disease states. The authors describe the development of the first high-throughput screening assay for the discovery of inhibitors of methyl-lysine binding proteins that will be used to initiate a full-scale discovery effort for this broad target class. They focus on the development of an AlphaScreen™-based assay for malignant brain tumor (MBT) domain-containing proteins, which bind to the lower methylation states of lysine residues present in histone tail peptides. This assay takes advantage of the avidity of the AlphaScreen™ beads to clear the hurdle to assay development presented by the low micromolar binding constants of the histone binding proteins for their cognate peptides. The assay is applicable to other families of methyl-lysine binding proteins, and it has the potential to be used in screening efforts toward the discovery of novel small molecules with utility as research tools for cellular reprogramming and ultimately drug discovery.

scholarly journals Molecular Basis of Histone Tail Recognition by Human TIP5 PHD Finger and Bromodomain of the Chromatin Remodeling Complex NoRC

Structure ◽  
2015 ◽  
Vol 23 (1) ◽  
pp. 80-92 ◽  
Author(s):  
Cynthia Tallant ◽  
Erica Valentini ◽  
Oleg Fedorov ◽  
Lois Overvoorde ◽  
Fleur M. Ferguson ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Molecular Basis ◽  
Histone Tail ◽  
Phd Finger ◽  
Chromatin Remodeling Complex

scholarly journals Competitive Binding of a Benzimidazole to the Histone-Binding Pocket of the Pygo PHD Finger

2014 ◽  
Vol 9 (12) ◽  
pp. 2864-2874 ◽  
Author(s):  
Thomas C. R. Miller ◽  
Trevor J. Rutherford ◽  
Kristian Birchall ◽  
Jasveen Chugh ◽  
Marc Fiedler ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Competitive Binding ◽  
Histone Binding ◽  
Phd Finger

scholarly journals Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b

Nature ◽  
2010 ◽  
Vol 466 (7303) ◽  
pp. 258-262 ◽  
Author(s):  
Lei Zeng ◽  
Qiang Zhang ◽  
SiDe Li ◽  
Alexander N. Plotnikov ◽  
Martin J. Walsh ◽  
...  
Keyword(s):  
Histone Binding ◽  
Phd Finger

scholarly journals The BRPF1 bromodomain is a molecular reader of di-acetyllysine

2020 ◽  
Author(s):  
Juliet O. Obi ◽  
Mulu Y. Lubula ◽  
Gabriel Cornilescu ◽  
Amy Henrickson ◽  
Kara McGuire ◽  
...  
Keyword(s):  
Zinc Finger Protein ◽  
Analytical Ultracentrifugation ◽  
Binding Pocket ◽  
Histone H4 ◽  
Histone Tail ◽  
Tail Region ◽  
Pwwp Domain ◽  
Altered Expression ◽  
Phd Finger ◽  
Finger Protein

ABSTRACTBromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. BRPF1 is known to recruit the MOZ HAT complex to chromatin by recognizing acetylated lysine residues on the N-terminal histone tail region through its bromodomain. However, histone proteins can contain several acetylation modifications on their N-terminus, and it is unknown how additional marks influence bromodomain recruitment to chromatin. Here, we identify the BRPF1 bromodomain as a selective reader of di-acetyllysine modifications on histone H4. We used ITC assays to characterize the binding of di-acetylated histone ligands to the BRPF1 bromodomain and found that the domain binds preferentially to histone peptides H4K5acK8ac and H4K5acK12ac. Analytical ultracentrifugation (AUC) experiments revealed that the monomeric state of the BRPF1 bromodomain coordinates di-acetylated histone ligands. NMR chemical shift perturbation studies, along with binding and mutational analyses, revealed non-canonical regions of the bromodomain-binding pocket that are important for histone tail recognition. Together, our findings provide critical information on how the combinatorial action of post-translational modifications can modulate BRPF1 bromodomain binding and specificity.

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