Atypical histone targets of PHD fingers

Black, JoshuaC.; Kutateladze, Tatiana G.

doi:10.1016/j.jbc.2023.104601

Cited by 15 publications

(9 citation statements)

References 62 publications

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“…S6B,D, Table S3), however none of them was specific to H3. PHD fingers have been reported to bind non-H3 partners, like DNA, histone 4, or other proteins (Bienz, 2006; Black & Kutateladze, 2023; Gaurav & Kutateladze, 2023; L. Liu et al, 2012; Oppikofer et al, 2017). The combination of the PHD and PHD-zinc-finger-like domain in the DevPFs may enable the paralogs to simultaneously recognize two adjacent histone modifications, as demonstrated for tandem PHD domains (Zeng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Two paralogous PHD finger proteins participate inParamecium tetraurelia’s natural genome editing

Häußermann,

Singh,

Swart

2024

Preprint

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The unicellular eukaryoteParamecium tetraureliacontains functionally distinct nuclei: germline micronuclei (MICs) and a somatic macronucleus (MAC). During sexual reproduction, the MIC genome is reorganized into a new MAC genome and the old MAC is lost. Almost 45,000 unique Internal Eliminated Sequences (IESs) distributed throughout the genome require precise excision to guarantee a functional new MAC genome. Here, we characterize a pair of paralogous PHD finger proteins involved in DNA elimination. DevPF1, the early-expressed paralog, is present in only some of the gametic and post-zygotic nuclei during meiosis. Both DevPF1 and DevPF2 localize in the new developing MACs, where IESs excision occurs. InDevPF2knockdown (KD) long IESs are preferentially retained and late-expressed small RNAs decrease; no length preference for retained IESs was observed inDevPF1-KD and development-specific small RNAs were abolished. The expression of at least two genes from the new MAC with roles in genome reorganization seems to be influenced byDevPF1-andDevPF2-KD. Thus, both PHD fingers are crucial for new MAC genome development, with distinct functions, potentially via regulation of non-coding and coding transcription in the MICs and new MACs.

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Section: Discussionmentioning

confidence: 99%

Section: Implications Of the Phd Domain For Devpf1 And Devpf2 Functionsmentioning

confidence: 99%

Two paralogous PHD finger proteins participate inParamecium tetraurelia’s natural genome editing

Häußermann,

Singh,

Swart

2024

Preprint

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“…Another potential avenue of treatment options targeting epigenetic players is plant homeodomain (PHD) co-fingers, found, for example, in KDM5A, a reader/effector protein activated by the PI3K/AKT pathway and acting on H3K4me3, as previously detailed above [52]. There is some pre-clinical evidence based on small in vitro studies suggesting that KDM5A, via PHD3, could be inhibited by already-FDA-approved agents, including amiodarone derivatives and disulfiram, as well as novel small molecule cyclopeptides [83][84][85]. Further studies are necessary, however, to prove the clinical efficacy, safety regarding therapeutic windows, and adverse effects of this new indication, and the feasibility of the administration of these agents as PHD finger inhibitors and epigenetic modulators.…”

Section: Exploration Of Potential Epigenetics-based Biomarkers For No...mentioning

confidence: 93%

The Promise of Epigenetics Research in the Treatment of Appendiceal Neoplasms

Ladel,

Tan,

Jeyakanthan

et al. 2023

Cells

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Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have marked differences in biological behavior and treatment response, and evidence suggests significant discrepancies in their respective genetic profiles. In addition, while the WHO classification for appendiceal cancers is currently based on traditional histopathological criteria, studies have demonstrated that histomorphology does not correlate with survival or treatment response in AC. Due to their rarity, appendiceal cancers have not been studied as extensively as other gastrointestinal cancers. However, their incidence has been increasing steadily over the past decade, making it crucial to identify new and more effective strategies for detection and treatment. Recent efforts to map and understand the molecular landscape of appendiceal cancers have unearthed a wealth of information that has made it evident that appendiceal cancers possess a unique molecular profile, distinct from other gastrointestinal cancers. This review focuses on the epigenetic landscape of epithelial appendiceal cancers and aims to provide a comprehensive overview of the current state of knowledge of epigenetic changes across different appendiceal cancer subtypes, highlighting the challenges as well as the promise of employing epigenetics in the quest for the detection of biomarkers, therapeutic targets, surveillance markers, and predictors of treatment response and survival in epithelial appendiceal neoplasms.

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“…Plant homeodomain (PHD) fingers are a class of chromatin readers that recognize specific lysine residues in chromatin as a function of the methylation state, although a subset of PHD fingers can also discriminate their histone ligands based on other interactions (e.g., lysine acylation, presence of arginine). 1,2 PHD fingers are small domains consisting of B50-80 amino acids, typically Cys 4 -His-Cys 3 zinc fingers, and are often found on proteins containing other PHD fingers, bromodomains, chromodomains, or Tudor domains that may contribute to multivalent histone recognition. 1,3 In the context of PHD fingers, the specificity to the methylation state of lysine arises from the structure of the binding pocket.…”

Section: Introductionmentioning

confidence: 99%

“…, lysine acylation, presence of arginine). 1,2 PHD fingers are small domains consisting of ∼50–80 amino acids, typically Cys 4 -His-Cys 3 zinc fingers, and are often found on proteins containing other PHD fingers, bromodomains, chromodomains, or Tudor domains that may contribute to multivalent histone recognition. 1,3 In the context of PHD fingers, the specificity to the methylation state of lysine arises from the structure of the binding pocket.…”

Section: Introductionmentioning

confidence: 99%