ASF1A
- Known as:
- ASF1A
- Catalog number:
- Y213818
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ASF1A
Related genes to: ASF1A
- Gene:
- ASF1A NIH gene
- Name:
- anti-silencing function 1A histone chaperone
- Previous symbol:
- -
- Synonyms:
- DKFZP547E2110, CIA
- Chromosome:
- 6q22.31
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-01
- Date modifiied:
- 2015-09-11
Related products to: ASF1A
Related articles to: ASF1A
- Amyotrophic lateral sclerosis (ALS) is characterised by the aggregation of TDP-43 and mutant FUS in the cytoplasm of affected motor neurons. Accumulation of DNA damage is emerging as a novel correlative trait of ALS. We recently showed that formation of TDP-43 and FUS cytoplasmic inclusions (CIs) lead to DNA damage accumulation through dysregulation of the DNA damage response (DDR). However, the multiple molecular mechanisms contributing to DNA damage accumulation in affected motor neurons in ALS have not been fully elucidated. In recent years, chemical inhibition of the serine/threonine kinase CHK1 was shown to lead to accumulation of DNA breaks as well as increased apoptosis, in differentiated cortical neurons. Notably, CHK1 has been involved in DNA double-strand break repair in non-dividing cells, by acting through the histone chaperone ASF1A. In this article, we show that cells bearing FUS and TDP-43 CIs show downregulation of the protein levels of CHK1 and ASF1A. We observe CHK1 protein downregulation in neuronal cell lines, as well as in patient-derived motor neurons progenitors and in the spinal cord of a FUS-ALS mouse model. Restoration of the nuclear levels of CHK1 and ASF1A via transient overexpression, is sufficient to reduce DNA damage signal accumulation and rescues DDR defects. Importantly, we show that the ubiquitin-proteasome pathway is responsible for CHK1 degradation in cells bearing FUS CI, since its inhibition restores CHK1 and ASF1A protein levels. Our study demonstrates that proteasomal-dependent CHK1 and ASF1A downregulation contributes to accumulation of DNA damage in cells affected by ALS-linked protein aggregates. - Source: PubMed
Publication date: 2026/05/06
Modafferi StefaniaSilenzi ValentinaGarbelli AnnaLazoi GloriaScarian EveljnD'Uva SaraSantini TizianaRiccardi AdelaideCozzolino MauroPansarasa OriettaD'Ambrosi NadiaSabbioneda SimoneMorlando MariangelaFrancia Sofia - Glioblastoma (GBM) is characterized by pronounced tumor heterogeneity and a complex immune microenvironment, contributing to poor patient survival outcomes. In this study, we comprehensively dissected the tumor microenvironment (TME) and uncovered potential molecular mechanisms by integrating single-cell, bulk, and spatial transcriptomic data. Hallmarks of malignancy and cell cycle regulatory pathways were consistently enriched across these modalities, promoting tumor cell proliferation and progression. Using machine learning algorithm, we identified seven hallmark-related prognostic signatures (HMsig), namely AEBP1, ASF1A, PRPS1, DCC, OPHN1, IL13RA2, and HDAC5-whose predictive importance was validated through SHAP analysis. Ligand-receptor (LR) interaction analysis further revealed that interactions involving OPHN1 were associated with poorer prognosis. Along the pseudotime trajectory of T-cell differentiation, immune checkpoint genes (ICGs) LAG3, PDCD1, and HAVCR2 were substantially upregulated. Notably, synergistic transcriptional regulation between tumor-related HMsig genes and ICGs in T cells was identified as a key factor influencing patient survival. Spatial transcriptomic analysis demonstrated the existence of synergistic gene interactions, deciphering the immunomodulatory functions of GBM biomarkers within the TME. - Source: PubMed
Publication date: 2026/03/25
Li TengyueMi WanqiYan HuaruiMa YiningJiang HanYang XiaoxuZhang YunpengHu Congxue - Extrachromosomal DNAs (ecDNAs) play an important role in tumor progression. ecDNA hubs have been shown to be anchored by BRD4, a chromatin reader. However, the chromatin organization of ecDNA hub remains unknown. Here we show that histone 3 lysine 56 acetylation (H3K56ac) mark binds to BRD4 specifically. Knockdown of BRD4 decreased the ecDNA hub signals by the ecTag method. Knockdown of an epigenetic player (USP7), histone acetyltransferase (CBP), or histone chaperone (Asf1a) that regulates H3K56ac mark also decreased ecDNA hub signals and H3K56ac levels, supporting the role of H3K56ac in regulating ecDNA hub maintenance. Co-immunoprecipitation experiments showed the interactions of BRD4, USP7, Asf1a, and CBP. Analysis of ChIP-seq datasets showed that both H3K56ac and H3K27ac converged with BRD4 binding at the ecDNA-chromosome interaction sites and ecDNA itself. However, H3K56ac had a widespread enrichment with most BRD4-occupied sites compared with H3K27ac that occupied a limited subset of BRD4 peaks. These results present a framework of ecDNA hub chromatin organization that maintains ecDNA hub integrity, further providing therapeutic options that could be used to target ecDNA hubs. - Source: PubMed
Publication date: 2026/01/06
Liao Li-ZhuWu Chang-JiunChen Yu-AnLin Tzu-ChinLin Po-HungWei Chia-LinWu Kou-Juey - PML nuclear bodies (PML-NBs) are dynamic subnuclear structures important for chromatin dynamics and anti-viral defense. In this study we investigate the role of Sp100 isoforms in promoting localization of the H3.3 histone chaperone HIRA to PML-NBs in human keratinocytes. Sp100 knockout (KO) cell lines were generated in normal keratinocytes using CRISPR-Cas9 technology and shown to display typical skin development, normal PML-NB formation, and a normal interferon response as determined by RNAseq. However, the histone chaperone HIRA and its associated complex members (Ubinuclein-1 and ASF1A) failed to localize to PML-NBs in the absence of Sp100, even after interferon stimulation. Exogenous expression of the four main isoforms of Sp100 showed that the Sp100A isoform is the primary driver of HIRA localization to PML-NBs; predictive structural analysis of the various Sp100 isoforms using several AI methods (AlphaFold 3, Chai-1, and Boltz-2) plus molecular dynamics simulation of Sp100B highlighted how interspersed structural domains and intrinsically disordered regions (IDRs) could influence this localization. Analysis of Sp100A proteins with mutations in seven distinct functions showed that the SUMO-interacting motif (SIM) plays an important role in HIRA localization to PML-NBs. These findings highlight the functional diversity of the Sp100 isoforms in modulating chromatin dynamics at PML-NBs and further discern the molecular features underpinning the relationship between histone chaperones and PML-NBs. We conclude that HIRA recruitment to PML-NBs is not required for immediate interferon signaling but as suggested by others, is potentially required for maintaining epigenetic memory by delayed H3.3 incorporation at interferon-stimulated genes. - Source: PubMed
Publication date: 2025/10/13
Della Fera Ashley NArman WardaPowers Maceo ECachau Raul EWarburton AlixMcBride Alison A - PML nuclear bodies (PML-NBs) are dynamic subnuclear structures important for chromatin dynamics and anti-viral defense. In this study we investigate the role of Sp100 isoforms in promoting localization of the H3.3 histone chaperone HIRA to PML-NBs in human keratinocytes. Sp100 knockout (KO) cell lines were generated using CRISPR-Cas9 technology and shown to display normal keratinocyte differentiation and PML-NB formation. However, HIRA and its associated complex members (UBN1 and ASF1a) failed to localize to PML-NBs in the absence of Sp100, even after interferon stimulation. Exogenous expression of the four main isoforms of Sp100 showed that the Sp100A isoform is the primary driver of HIRA localization to PML-NBs, with the SUMO interacting motif (SIM) playing an important role. These findings highlight the functional diversity of the Sp100 isoforms in modulating chromatin dynamics at PML-NBs. - Source: PubMed
Publication date: 2025/03/06
Della Fera Ashley NArman WardaPowers Maceo EWarburton AlixMcBride Alison A