Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells

Redon, Christophe E.; Schmal, Zoé; Tewary, Gargi; Mangelinck, Adèle; Courbeyrette, Régis; Thuret, Jean‐Yves; Aladjem, Mirit I.; Bonner, William M.; Rübe, Claudia E.; Mann, Carl

doi:10.3390/genes12111665

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…We showed the overexpression of ten immunomodulatory peptides in gene level of BC epithelial cells versus normal and validated these results in chromatin level. The elevated expression of these AMPs in BC is also reported previously (30, 34, 35, 39, 40, 43, 44, 57, 58). However, the therapetuic use of these peptide against BC by manipulationg their expression is yet to be explored.…”

Section: Discussionsupporting

confidence: 86%

Drug repositioning for immunotherapy in breast cancer using single-cell and spatial transcriptomics analysis

Mohammadi

Jin

Zhang

et al. 2022

Preprint

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Immunomodulatory peptides are capable of stimulating or suppressing the immune system. Hence, deregulation of them can be considered as an immunotherapy approach. These peptides may have dual behavior in response to different infections. For instance, an antimicrobial peptide may act as an anticancer, tumor marker or even cause cancer progression. In this study, we used single-cell RNA sequencing analysis to investigate the deregulation of immunomodulatory peptides in malignant versus normal human breast epithelial cells. We validated the obtained results in chromatin accessibility level. Furthermore, we used a drug repositioning approach to change the expression of these peptides based on their role in cancer biology. As a result, ten immunomodulatory peptides were upregulated in breast cancer versus normal. Chromatin was more accessible for these peptides in cancer cell lines versus normal. Among these ten peptides, five of them were tumor drivers (i.e., BST2, GAPDH, S100A8, S100A9 and HMGB1), three of them were anticancer (i.e., H2AFJ, SCGB2A1 and HMGN2), S100A7 had dual behavior in different cancers and ZG16B was a tumor marker. Using the LINCS L1000 database, we proposed a list of drugs that can deregulate the candidate peptides according to their role in the progression of malignancy. In conclusion, immunomodulatory peptides can be considered as drug targets based on their role in cancer biology.

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Section: Discussionsupporting

confidence: 86%

Drug repositioning for immunotherapy in breast cancer using single-cell and spatial transcriptomics analysis

Mohammadi

Jin

Zhang

et al. 2022

Preprint

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“…Previous studies noted organ-specific differences in H2A.J protein expression in normal tissues generally, with strong labeling of luminal epithelial cells, even without IR exposure [ 27 ]. Here, we used IFM to visualize H2A.J expression within different cell types in lung tissue of mice exposed to different doses of IR.…”

Section: Resultsmentioning

confidence: 99%

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

Al-razaq

Freyter

Isermann

et al. 2023

Cells

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Purpose: Radiation-induced senescence is characterized by profound changes in chromatin organization with the formation of Senescence-Associated-Heterochromatin-Foci (SAHF) and DNA-Segments-with-Chromatin-Alterations-Reinforcing-Senescence (DNA-SCARS). Importantly, senescent cells also secrete complex combinations of pro-inflammatory factors, referred as Senescence-Associated-Secretory-Phenotype (SASP). Here, we analyzed the epigenetic mechanism of histone variant H2A.J in establishing radiation-induced senescence. Experimental Design: Primary and genetically-modified lung fibroblasts with down- or up-regulated H2A.J expression were exposed to ionizing radiation and were analyzed for the formation of SAHF and DNA-SCARS by immunofluorescence microscopy. Dynamic changes in chromatin organization and accessibility, transcription factor recruitment, and transcriptome signatures were mapped by ATAC-seq and RNA-seq analysis. The secretion of SASP factors and potential bystander effects were analyzed by ELISA and RT-PCR. Lung tissue of mice exposed to different doses were analyzed by the digital image analysis of H2A.J-immunohistochemistry. Results: Differential incorporation of H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of senescence. Integrative analyses of ATAC-seq and RNA-seq datasets indicate that H2A.J-associated changes in chromatin accessibility of regulatory regions decisively modulates transcription factor recruitment and inflammatory gene expression, resulting in an altered SASP secretome. In lung parenchyma, pneumocytes show dose-dependent H2A.J expression in response to radiation-induced DNA damage, therefore contributing to pro-inflammatory tissue reactions. Conclusions: The fine-tuned incorporation of H2A.J defines the epigenetic landscape for driving the senescence programme in response to radiation-induced DNA damage. Deregulated H2A.J deposition affects chromatin remodeling, transcription factor recruitment, and the pro-inflammatory secretome. Our findings provide new mechanistic insights into DNA-damage triggered epigenetic mechanisms governing the biological processes of radiation-induced injury.

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“…Indeed, the fucosylation and sialylation inhibitor pictilisib affected the DNA repair capacity of lung cancer cells . The histone H2AFJ (cluster e) is usually expressed in luminal epithelial cells, although its role is still poorly understood . However, it was recently found that high H2AFJ expression in CRC cells correlated with a significantly worse prognosis and acquired chemoradiation resistance .…”

Section: Discussionmentioning

confidence: 99%

“… 114 The histone H2AFJ (cluster e) is usually expressed in luminal epithelial cells, although its role is still poorly understood. 115 However, it was recently found that high H2AFJ expression in CRC cells correlated with a significantly worse prognosis and acquired chemoradiation resistance. 116 Interestingly, this group of proteins also revealed other specimens with an important role in the cellular response to radiotherapy, such as XRCC5 and XRCC6.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Mass Spectrometry Analysis of N-Glycans and Protein Markers after FUT8 Knockdown in the Syngeneic SW480/SW620 Colorectal Cancer Cell Model

López-Cortés,

Muinelo-Romay,

Fernández-Briera

et al. 2024

J. Proteome Res.

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Disruption of the glycosylation machinery is a common feature in many types of cancer, and colorectal cancer (CRC) is no exception. Core fucosylation is mediated by the enzyme fucosyltransferase 8 (FucT-8), which catalyzes the addition of α1,6-L-fucose to the innermost GlcNAc residue of N-glycans. We and others have documented the involvement of FucT-8 and core-fucosylated proteins in CRC progression, in which we addressed core fucosylation in the syngeneic CRC model formed by SW480 and SW620 tumor cell lines from the perspective of alterations in their N-glycosylation profile and protein expression as an effect of the knockdown of the FUT8 gene that encodes FucT-8. Using label-free, semiquantitative mass spectrometry (MS) analysis, we found noticeable differences in N-glycosylation patterns in FUT8-knockdown cells, affecting core fucosylation and sialylation, the Hex/HexNAc ratio, and antennarity. Furthermore, stable isotopic labeling of amino acids in cell culture (SILAC)-based proteomic screening detected the alteration of species involved in protein folding, endoplasmic reticulum (ER) and Golgi post-translational stabilization, epithelial polarity, and cellular response to damage and therapy. This data is available via ProteomeXchange with identifier PXD050012. Overall, the results obtained merit further investigation to validate their feasibility as biomarkers of progression and malignization in CRC, as well as their potential usefulness in clinical practice.

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Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells

Cited by 10 publications

References 43 publications

Drug repositioning for immunotherapy in breast cancer using single-cell and spatial transcriptomics analysis

Drug repositioning for immunotherapy in breast cancer using single-cell and spatial transcriptomics analysis

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

High-Throughput Mass Spectrometry Analysis of N-Glycans and Protein Markers after FUT8 Knockdown in the Syngeneic SW480/SW620 Colorectal Cancer Cell Model

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