Deacetylation of H4 lysine16 affects acetylation of lysine residues in histone H3 and H4 and promotes transcription of constitutive genes

Ray, Anagh; Khan, Preeti; Chaudhuri, Ronita Nag

doi:10.1080/15592294.2020.1809896

Cited by 10 publications

(4 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deacetylation is also linked directly to gene transcription. H4K16 deacetylation is required for regulating transcription activation and promotes regional gene expression 28 . STAT3 is involved in the pathology of asthma 20 .…”

Section: Discussionmentioning

confidence: 99%

The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation

Yu¹,

Huang²,

Huang³

et al. 2023

Theranostics

View full text Add to dashboard Cite

Background: Perturbation of macrophage homeostasis is one of the key mechanisms of airway inflammation in asthma. However, the exact mechanisms remain poorly understood. Objectives: We sought to examine the role of histone deacetylase (HDAC) 10 as an epigenetic regulator that governs macrophage M2 program and promotes airway inflammation in asthma, and to elucidate the underlying mechanisms. Methods: Peripheral blood and airway biopsies were obtained from healthy individuals and asthmatic patients. Asthma was induced by exposure to allergen in mice with myeloid-specific deletion of Hdac10 (Hdac10 fl/fl -LysMCre) mice. HDAC10 inhibitor Salvianolic acid B (SAB), STAT3 selective agonist Colivelin, and the specific PI3K/Akt activator 1,3-Dicaffeoylquinic acid (DA) were also used in asthmatic mice. For cell studies, THP1 cells, primary mouse bone marrow derived macrophage (BMDMs) were used and related signaling pathways was investigated. Results: HDAC10 expression was highly expressed by macrophages and promoted M2 macrophage activation and airway inflammation in asthmatic patients and mice. Hdac10 fl/fl -LysMCre mice were protected from airway inflammation in experimental asthma model. Hdac10 deficiency significantly attenuated STAT3 expression and decreased M2 macrophage polarization following allergen exposure. Mechanistically, HDAC10 directly binds STAT3 for deacetylation in macrophages, by which it promotes STAT3 expression and activates the macrophage M2 program. Importantly, we identified SAB as a HDAC10 inhibitor that had protective effects against airway inflammation in mice. Conclusions: Our results revealed that HDAC10-STAT3 interaction governs macrophage polarization to promote airway inflammation in asthma, implicating HDAC10 as a therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation

Yu¹,

Huang²,

Huang³

et al. 2023

Theranostics

View full text Add to dashboard Cite

show abstract

“…H4K16 deacetylation is required for regulating transcription activation and promotes regional gene expression 42 . Activated SIRT1 deacetylates PGC-1α and subsequently promotes PPARα transcriptional activity, resulting in enhanced HBV replication 43 . In our study, we found that K192 deacetylation of RORγt by SIRT6 induced the recruitment of RORγt to the IL-17A promoter.…”

Section: Discussionmentioning

confidence: 99%

Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling

Quan,

Wen,

et al. 2023

Nat Commun

View full text Add to dashboard Cite

Dysregulation of IL-17A is closely associated with airway inflammation and remodeling in severe asthma. However, the molecular mechanisms by which IL-17A is regulated remain unclear. Here we identify epithelial sirtuin 6 (SIRT6) as an epigenetic regulator that governs IL-17A pathogenicity in severe asthma. Mice with airway epithelial cell-specific deletion of Sirt6 are protected against allergen-induced airway inflammation and remodeling via inhibiting IL-17A-mediated inflammatory chemokines and mesenchymal reprogramming. Mechanistically, SIRT6 directly interacts with RORγt and mediates RORγt deacetylation at lysine 192 via its PPXY motifs. SIRT6 promotes RORγt recruitment to the IL-17A gene promoter and enhances its transcription. In severe asthma patients, high expression of SIRT6 positively correlates with airway remodeling and disease severity. SIRT6 inhibitor (OSS_128167) treatment significantly attenuates airway inflammation and remodeling in mice. Collectively, these results uncover a function for SIRT6 in regulating IL-17A pathogenicity in severe asthma, implicating SIRT6 as a potential therapeutic target for severe asthma.

show abstract

“…Histone acetylation is controlled by acetyltransferases (HATs) that transfer acetyl groups from acetyl co-enzyme A to lysine residues of the N-terminal H3 and H4 tails [ 23 , 24 ]. Consequently, the positive charge of histone is neutralized, which reduces chromatin condensation, allowing the initialization of gene transcription [ 25 ].…”

Section: The Mechanism Of Epigenetic Modificationsmentioning

confidence: 99%

Mesenchymal stem cells under epigenetic control – the role of epigenetic machinery in fate decision and functional properties

Walewska,

Janucik,

Tynecka

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Mesenchymal stem cells (mesenchymal stromal cells, MSC) are multipotent stem cells that can differentiate into cells of at least three mesodermal lineages, namely adipocytes, osteoblasts, and chondrocytes, and have potent immunomodulatory properties. Epigenetic modifications are critical regulators of gene expression and cellular differentiation of mesenchymal stem cells (MSCs). Epigenetic machinery controls MSC differentiation through direct modifications to DNA and histones. Understanding the role of epigenetic machinery in MSC is crucial for the development of effective cell-based therapies for degenerative and inflammatory diseases. In this review, we summarize the current understanding of the role of epigenetic control of MSC differentiation and immunomodulatory properties.

show abstract

Deacetylation of H4 lysine16 affects acetylation of lysine residues in histone H3 and H4 and promotes transcription of constitutive genes

Cited by 10 publications

References 112 publications

The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation

The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation

Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling

Mesenchymal stem cells under epigenetic control – the role of epigenetic machinery in fate decision and functional properties

Contact Info

Product

Resources

About