Modifying Chromatin by Histone Tail Clipping

Azad, Gajendra Kumar; Swagatika, Swati; Kumawat, Manoj; Kumawat, Ramesh; Tomar, Raghuvir Singh

doi:10.1016/j.jmb.2018.07.013

Cited by 38 publications

(25 citation statements)

References 160 publications

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“…To date, clipping of the H3 tail has been observed in eukaryotic organisms from yeast to human (Santos-Rosa et al, 2009;Khalkhali-Ellis et al, 2014;Vossaert et al, 2014), has been implicated in several biological contexts such as embryonic stem cell differentiation, cellular senescence and stress response (Duncan et al, 2008;Duarte et al, 2014;Shen et al, 2017), and has been shown to impact nuclear processes from transcription to chromatin compaction (Santos-Rosa et al, 2009;Nurse et al, 2013;Duarte et al, 2014). Despite this diversity, little is known about the mechanisms upstream of histone tail removal, and its physiological significance in mammalian cells remains largely elusive (Azad et al, 2018;Yi and Kim, 2018). In the present study, we show that lack of the cysteine protease inhibitor CSTB leads to disproportionate cleavage of histone H3 in cells of the neural lineage.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy

Daura

Tegelberg

Yoshihara

et al. 2020

Preprint

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“…A more drastic change is the is histone proteolysis or clipping, where the N terminal tail is irreversible cleaved by intracellular proteases. It is a phenomenon that has been observed from yeast to mammal and regulates many biological functions (6,57,58). For example, histone H3 clipping was found to regulate differentiation of human stem cells (59) and observed in human cancer (60).…”

Section: Middle-down Proteomicsmentioning

confidence: 99%

Accelerating the Field of Epigenetic Histone Modification Through Mass Spectrometry–Based Approaches

Coradin

Porter

et al. 2021

Molecular & Cellular Proteomics

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Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Due to its high-throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology and biophysics, MS has been employed to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology.

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“…For a perspective on recent advances on higher‐order structures of chromatin and their implications on the regulation of gene expression, see Bascom and Schlick, Grigoryev, and Rowley and Corces (3C technologies) . Noteworthy biological perspectives on histone post‐translational modifications are by Andrews et al and Azad et al and on LH binding modes and their roles in the regulation of chromatin structure and function by Öztürk et al and Fyodorov et al…”

Section: Overview: Molecular Modeling To Interpret Genome Contact Andmentioning

confidence: 99%

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

Portillo‐Ledesma

Schlick

2019

WIREs Comput Mol Sci

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Chromatin structure, dynamics, and function are being intensely investigated by a variety of methods, including microscopy, X‐ray diffraction, nuclear magnetic resonance, biochemical crosslinking, chromosome conformation capture, and computation. The modeling helps interpret experimental data and generate configurations and mechanisms related to the three‐dimensional organization and function of the genome. Experimental contact maps, in particular, as obtained by a variety of chromosome conformation capture methods, are of increasing interest due to their implications on genome structure and regulation on many levels. In this perspective, using seven examples from our group's studies, we illustrate how molecular modeling can help interpret such experimental data. Specifically, we show how computed contact maps related to experimental systems can help interpret structures of nucleosomes, chromatin higher‐order folding, domain segregation mechanisms, gene organization, and the effect on chromatin structure of external and internal fiber parameters, such as nucleosome positioning, presence of nucleosome free regions, histone post‐translational modifications, and linker histone binding. We argue that such computations on multiple spatial and temporal scales will be increasingly important for the integration of genomic, epigenomic, and biophysical data on chromatin structure and related cellular processes. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics

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Modifying Chromatin by Histone Tail Clipping

Cited by 38 publications

References 160 publications

Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy

Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy

Accelerating the Field of Epigenetic Histone Modification Through Mass Spectrometry–Based Approaches

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

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