Biochemical Analysis Reveals the Multifactorial Mechanism of Histone H3 Clipping by Chicken Liver Histone H3 Protease

Chauhan, Sakshi; Mandal, Papita; Tomar, Raghuvir Singh

doi:10.1021/acs.biochem.6b00625

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…Proteases play regulatory roles in epigenetic mechanisms of altered gene expression. Various non-specific and N-tail specific histone proteases are thought to assist in fertilization, histone turnover, gene de-repression, histone removal during spermatogenesis, and reversal of N-tail methylation [86]. In N-tail clipped histone H3, lysines for acetylation have been removed, which may result in transcriptionally inactive chromatin.…”

Section: Proteases and Diseasementioning

confidence: 99%

Proteases: Pivot Points in Functional Proteomics

Verhamme

Leonard

Perkins

2018

Functional Proteomics

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Proteases drive the life cycle of all proteins, ensuring the transportation and activation of newly minted, would-be proteins into their functional form while recycling spent or unneeded proteins. Far from their image as engines of protein digestion, proteases play fundamental roles in basic physiology and regulation at multiple levels of systems biology. Proteases are intimately associated with disease and modulation of proteolytic activity is the presumed target for successful therapeutics. “Proteases: Pivot Points in Functional Proteomics” examines the crucial roles of proteolysis across a wide range of physiological processes and diseases. The existing and potential impacts of proteolysis-related activity on drug and biomarker development are presented in detail. All told the decisive roles of proteases in four major categories comprising 23 separate sub-categories are addressed. Within this construct, 15 sets of subject-specific, tabulated data are presented that include identification of proteases, protease inhibitors, substrates and their actions. Said data are derived from and confirmed by over 300 references. Cross comparison of datasets indicates that proteases, their inhibitors/promoters and substrates intersect over a range of physiological processes and diseases, both chronic and pathogenic. Indeed, “Proteases: Pivot Points …” closes by dramatizing this very point through association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity, cardiovascular and metabolic disease, cancer, neurodegeneration and bacterial self-defense.

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Section: Proteases and Diseasementioning

confidence: 99%

Proteases: Pivot Points in Functional Proteomics

Verhamme

Leonard

Perkins

2018

Functional Proteomics

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“…Within the cell, CSTB localizes to the nucleus and the cytosol, where it is associated with a subset of lysosomes (Riccio et al, 2001;Brännvall et al, 2003;Alakurtti et al, 2005). In the nucleus, CSTB interacts with cathepsin L (Ceru et al, 2010;Chauhan et al, 2016), a protease with several reported nuclear functions including regulation of cell cycle progression through proteolytic processing of CDP/Cux transcription factor, stabilization of epigenetic heterochromatin markers, sperm histone degradation, and histone H3 tail clipping (Goulet et al, 2004;Bulynko et al, 2006;Duncan et al, 2008;Adams-Cioaba et al, 2011;Morin et al, 2012). Cathepsin L is one of several intracellular proteases that have emerged as epigenetic regulators through their ability to remove histone tails, particularly during cell-state transitions (e.g.…”

Section: Introductionmentioning

confidence: 99%

Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy

Daura

Tegelberg

Yoshihara

et al. 2020

Preprint

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We establish cystatin B (CSTB) as a regulator of histone H3 tail clipping in murine neural progenitor cells (NPCs) and provide evidence suggesting that epigenetic dysregulation contributes to the early pathogenesis in brain disorders associated with deficient CSTB function. We show that NPCs undergo regulated cleavage of the N-terminal tail of histone H3 at threonine 22 (H3T22) transiently upon induction of differentiation. CSTB-deficient NPCs present premature activation of H3T22 clipping during self-renewal mediated by increased activity of cathepsins L and B. During differentiation, the proportion of immature committed neurons undergoing H3T22 clipping is significantly higher in CSTB-deficient than in wild-type NPCs, with no observable decline within 12 days post-differentiation. CSTB-deficient NPCs exhibit significant transcriptional changes highlighting altered expression of nuclear-encoded mitochondrial genes. These changes are associated with significantly impaired respiratory capacity of differentiating NPCs devoid of CSTB. Our data expand the mechanistic understanding of diseases associated with CSTB deficiency.

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“… 4 The mouse H3t histone has a human counterpart, H3T (H3.4), and shares a common chaperon recognition motif with H3.1 and H3.2. 5 Knockout mice for H3t were first generated in 2017; both male and female H3t null mice were viable and healthy, but the male mice were sterile. 6 H3t deficiency leads to azoospermia because of the loss of haploid germ cells.…”

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confidence: 99%