Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions

Jain, Kanishk; Fraser, Caroline S.; Marunde, Matthew R.; Parker, Madison M; Sagum, Cari A.; Burg, Jonathan M.; Hall, Nathan W.; Popova, Irina K; Rodriguez, Keli L.; Vaidya, Anup; Krajewski, Krzysztof; Keogh, Michael Christopher; Bedford, Mark T.; Strahl, Brian D.

doi:10.1186/s13072-020-0328-z

Cited by 87 publications

(76 citation statements)

References 43 publications

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“…As positive and negative controls, the histone H3K4me3 peptide interacted with known H3K4me3-interacting PHD finger domains and Tudor domains, while the unmodified peptide did not (Figure 2, top left panel). Interestingly, each of the seven peptide probes that harbored the K4me3 mark (Figure 2), displayed a unique interaction profile with known H3K4me3-interacting PHD finger domains (63), and many of these peptides also bound the Tudor domain-containing protein SPIN1, which is a well characterized H3K4me3 reader (64). The relative intensities of these interactions on the arrays were quantified (Figure S1).…”

Section: Identification Of H3tms Interactions With Methyllysine-effector Domainsmentioning

confidence: 99%

Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions

Chen

Horton

Sagum

et al. 2021

Biochemical Journal

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The reader ability of PHD fingers is largely limited to the recognition of the histone H3 N-terminal tail. Distinct subsets of PHDs bind either H3K4me3 (a transcriptional activator mark) or H3K4me0 (a transcriptional repressor state). Structural studies have identified common features among the different H3K4me3 effector PHDs, including 1) removal of the initiator methionine residue of H3 to prevent steric interference, 2) a groove where arginine-2 binds, and 3) an aromatic cage that engages methylated lysine-4. We hypothesize that PHDs have the ability to engage with non-histone ligands, as long as they adhere to these three rules. A search of the human proteome revealed an enrichment of chromatin-binding proteins that met these criteria, which we termed H3 N-terminal mimicry proteins (H3TMs). Seven H3TMs were selected, and used to screen a protein domain microarray for potential effector domains, and they all had the ability to bind H3K4me3-interacting effector domains. Furthermore, the binding affinity between the VRK1 peptide and the PHD domain of PHF2 is ~3-fold stronger than that of PHF2 and H3K4me3 interaction. The crystal structure of PHF2 PHD finger bound with VRK1 K4me3 peptide provides a molecular basis for stronger binding of VRK1 peptide. In addition, a number of the H3TMs peptides, in their unmethylated form, interact with NuRD transcriptional repressor complex. Our findings provide in vitro evidence that methylation of H3TMs can promote interactions with PHD and Tudor domain-containing proteins and potentially block interactions with the NuRD complex. We propose that these interactions can occur in vivo as well.

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Section: Identification Of H3tms Interactions With Methyllysine-effector Domainsmentioning

confidence: 99%

Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions

Chen

Horton

Sagum

et al. 2021

Biochemical Journal

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“…The plant homeodomain (PHD) fingers are central readers of PTMs that exist in more than 100 human proteins, many of which bind to unmodified or methylated H3K4. The PHD fingers play crucial roles in regulation of gene expression and carcinogenesis (Tsai et al, 2010;Zeng et al, 2010;Jain et al, 2020). It is shown that tripartite motif-containing protein 24 (TRIM24) functions as a reader of dual histone marks through tandem PHD and BRD domains (Tsai et al, 2010).…”

Section: Histone Methylation Readersmentioning

confidence: 99%

Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications

Wan

Zhang

Yao

et al. 2021

Front. Cell Dev. Biol.

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The involvement of histone modifications in cartilage development, pathology and regeneration is becoming increasingly evident. Understanding the molecular mechanisms and consequences of histone modification enzymes in cartilage development, homeostasis and pathology provides fundamental and precise perspectives to interpret the biological behavior of chondrocytes during skeletal development and the pathogenesis of various cartilage related diseases. Candidate molecules or drugs that target histone modifying proteins have shown promising therapeutic potential in the treatment of cartilage lesions associated with joint degeneration and other chondropathies. In this review, we summarized the advances in the understanding of histone modifications in the regulation of chondrocyte fate, cartilage development and pathology, particularly the molecular writers, erasers and readers involved. In addition, we have highlighted recent studies on the use of small molecules and drugs to manipulate histone signals to regulate chondrocyte functions or treat cartilage lesions, in particular osteoarthritis (OA), and discussed their potential therapeutic benefits and limitations in preventing articular cartilage degeneration or promoting its repair or regeneration.

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“…Оба PHD-домена, образуя единую структурную единицу, связывают один N-концевой фрагмент гистона H3 с модификацией H3K14ac, cr или bu [12,17,18] [12,14,17]. Появляется все больше экспериментальных данных о том, что второй PHD-домен белков d4 организован по тому же принципу и не узнает метилированный H3K4 [5].…”

Section: Dpf взаимодействуют с ацилированными H3k14 и H3k9unclassified

“…PHD-домены содержатся преимущественно в белках, взаимодействующих с N-концевыми фрагментами гистонов, они представляют собой регуляторы экспрессии генов [4]. PHD связываются с N-концевыми частями гистона H3, имеющего различные модификации [5,6].…”

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The DPF Domain As a Unique Structural Unit Participating in Transcriptional Activation, Cell Differentiation, and Malignant Transformation

et al. 2020

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The DPF (double PHD finger) domain consists of two PHD fingers organized in tandem. The two PHD-finger domains within a DPF form a single structure that interacts with the modification of the N-terminal histone fragment in a way different from that for single PHD fingers. Several histone modifications interacting with the DPF domain have already been identified. They include acetylation of H3K14 and H3K9, as well as crotonylation of H3K14. These modifications are found predominantly in transcriptionally active chromatin. Proteins containing DPF belong to two classes of protein complexes, which are the transcriptional coactivators involved in the regulation of the chromatin structure. These are the histone acetyltransferase complex belonging to the MYST family and the SWI/SNF chromatin-remodeling complex. The DPF domain is responsible for the specificity of the interactions between these complexes and chromatin. Proteins containing DPF play a crucial role in the activation of the transcription of a number of genes expressed during the development of an organism. These genes are important in the differentiation and malignant transformation of mammalian cells.

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Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions

Cited by 87 publications

References 43 publications

Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions

Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions

Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications

The DPF Domain As a Unique Structural Unit Participating in Transcriptional Activation, Cell Differentiation, and Malignant Transformation

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