Histone tail network and modulation in a nucleosome

Tsunaka, Yasuo; Furukawa, Ayako; Nishimura, Yoshifumi

doi:10.1016/j.sbi.2022.102436

Cited by 13 publications

(7 citation statements)

References 54 publications

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“…The trends described above support a shorter effective rotational correlation time and thus greater mobility on the ps-ns timescale in the two TGG repeats as compared to the remainder of the H3 tail, which extends into a more extensive 'hinge' region in residues ~S28-K36. This flexible 'hinge' has previously been noted (Furukawa et al, 2020;Morrison et al, 2021;Tsunaka et al, 2022). As a point of clarification regarding the difference between hnNOE and R2/R1 for V35 and K36, overall particle tumbling likely starts dominating near the core for R2/R1, leading to an observed decrease in ps-ns mobility at the C-terminal end of tail 'hinge'.…”

Section: Baseline Dynamics Of the H3 Tail Within Ncpmentioning

confidence: 53%

Arginine anchor points govern H3 tail dynamics

Jennings

Zoss

Morrison

2023

Front. Mol. Biosci.

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Chromatin is dynamically reorganized spatially and temporally, and the post-translational modification of histones is a key component of this regulation. The basic subunit of chromatin is the nucleosome core particle, consisting of two copies each of the histones H2A, H2B, H3, and H4 around which ∼147 base pairs of DNA wrap. The intrinsically disordered histone termini, or tails, protrude from the core and are heavily post-translationally modified. Previous studies have shown that the histone tails exist in dynamic ensembles of DNA-bound states within the nucleosome. Histone tail interactions with DNA are involved in nucleosome conformation and chromatin organization. Charge-modulating histone post-translational modifications (PTMs) are poised to perturb the dynamic interactions between histone tails and DNA. Arginine side chains form favorable interactions with DNA and are sites of charge-modulating PTMs such as citrullination. Our current focus is on the H3 tail, the longest histone tail. Four arginine residues are relatively evenly spaced along the H3 tail sequence, suggesting multivalent interactions with DNA poised for regulation by PTMs. In this study, we use NMR nuclear spin relaxation experiments to investigate the contribution of arginine residues to H3 tail dynamics within the nucleosome core particle. By neutralizing arginine via mutation to glutamine, we begin to work towards a comprehensive understanding of the contribution of individual residues to H3 tail dynamics. We find that neutralization of arginine residues results in increased regional mobility of the H3 tails, with implications for understanding the direct effects of arginine citrullination. Altogether, these studies support a role for dynamics within the histone language and emphasize the importance of charge-modulating histone PTMs in regulating chromatin dynamics, starting at the level of the basic subunit of chromatin.

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Section: Baseline Dynamics Of the H3 Tail Within Ncpmentioning

confidence: 53%

Arginine anchor points govern H3 tail dynamics

Jennings

Zoss

Morrison

2023

Front. Mol. Biosci.

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“…Approximately 146 base pairs of DNA are tightly wrapped around the histone octamer, rendering it generally inaccessible to TAFs (Fig. 2 A) 38 , 39 . Since the signal intensity of ChIP-seq profiles for histone H3 is low in the upstream of the TSS and TAFs are known to bind histone-free regions, it is predicted that the upstream of the TSS serves as the TAF-binding site (cis-regulatory element).…”

Section: Discussionmentioning

confidence: 99%

Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin

Li,

Nakamura

2023

Sci Rep

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The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.

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“…A growing number of studies suggest that SCFAs and short-chain fatty acylation contribute to CVD pathophysiology. Propionate, an SCFA, has been found to slow the progression of CVDs, in a manner potentially associated with enhanced protein propionylation [3]. Propionylation of H3K14 is enriched specifically in the gene active promoter region and significantly affects lipid metabolism in mice.…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

“…Nucleosome core particles are made of 146 bp of DNA wrapped 1.75 turns around a histone octamer [2]. During histone packaging, the N-terminal lysine and arginine-rich "tails" of histones protrude from the nucleosome ends and are the most prevalent sites of histone PTMs (HPTMs) [3]. HPTMs are essential in the epigenetic regulation of gene transcription, chromatin dynamics, DNA-damage repair, oxidative stress, cell metabolism, the cell cycle, cellular senescence, angiogenesis, and other key biological processes [4].…”

Section: Introductionmentioning

confidence: 99%

Biological functions and therapeutic potential of acylation by histone acetyltransferases

Li¹,

Hamor²,

An³

et al. 2023

Acta Materia Medica

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Histone lysine acylation is a major class of histone post-translational modifications involved in essential biological activities, such as transcriptional regulation, DNA-damage repair, and cell-cycle progression. Abnormal acylation is strongly associated with various diseases, such as cancer. Thus, histone acetyltransferases (HATs), the “writers” that catalyze histone acylation, are promising targets for cancer treatment. Rapid developments in structural biology and artificial intelligence have facilitated the development of drugs targeting HATs. To provide new ideas for exploring novel HAT modifiers with high efficiency and selectivity, this article reviews the relationships between acylation and diseases, illustrates HAT catalytic mechanisms through structural biology, and summarizes research progress in HAT modifiers.

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Histone tail network and modulation in a nucleosome

Cited by 13 publications

References 54 publications

Arginine anchor points govern H3 tail dynamics

Arginine anchor points govern H3 tail dynamics

Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin

Biological functions and therapeutic potential of acylation by histone acetyltransferases

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