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Review Open Access

ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review)

  • Authors:
    • Jun Yin
    • Xiaojian Zhuo
    • Lihui Wen
    • Xianmin Wang
    • Tongyong Luo
    • Qingsong Wang
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound, West China Hospital Sichuan University, Jintang First People's Hospital, Chengdu, Sichuan 610400, P.R. China, Public Relations Department, West China Hospital Sichuan University, Jintang First People's Hospital, Chengdu, Sichuan 610400, P.R. China, Department of Pediatrics, West China Hospital Sichuan University, Jintang First People's Hospital, Chengdu, Sichuan 610400, P.R. China, Pediatric Cardiology Center, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, Sichuan 610031, P.R. China
    Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 289
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    Published online on: September 2, 2026
       https://doi.org/10.3892/etm.2026.13284
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Abstract

Anti‑silencing function 1A (ASF1A) is an evolutionarily conserved histone H3/H4 chaperone that mediates nucleosome assembly, DNA replication and DNA damage repair. Beyond these canonical biological functions, aberrant ASF1A expression facilitates disease progression by triggering epigenetic dysregulation in multiple malignant tumors (including leukemia, breast, liver and gastrointestinal cancers) and non‑neoplastic disorders (such as atherosclerosis and embryonic developmental defects). Its context‑dependent biological effects are mediated via oncogenic signaling cascades and crosstalk between metabolism and epigenetics. Although preclinical studies have validated ASF1A as a promising prognostic biomarker and therapeutic target, relevant clinical trials supporting its clinical application remain absent. This review systematically summarizes the molecular features, pathogenic mechanisms and translational application potential of ASF1A.
View Figures

Figure 1

Domain architecture and
post-translational regulation of human ASF1A. The N-terminal core
(1-155 aa) binds H3.1-H4 and H3.3-H4 dimers and mediates mutually
exclusive delivery to the CAF-1 and HIRA complexes, respectively.
The intrinsically disordered C-terminal region (156-204 aa)
integrates regulatory inputs from TLK1/2-mediated phosphorylation,
USP52-dependent deubiquitination and p300/CBP-associated
acetylation. Ac, acetylation; P, phosphorylation; Ub,
ubiquitination; ASF1A, anti-silencing function 1A; aa, amino acids;
CAF-1, chromatin assembly factor 1; CBP, CREB-binding protein;
CDAN1, congenital dyserythropoietic anemia type 1; IDR,
intrinsically disordered region; HIRA, histone regulator A; TLK1/2,
Tousled-like kinase 1/2; USP52, ubiquitin-specific peptidase
52.

Figure 2

Context-dependent physiological
functions of ASF1A. ASF1A participates in replication-coupled and
replication-independent chromatin assembly, DNA damage repair via
homologous recombination and non-homologous end joining,
HIRA-mediated transcriptional regulation, embryonic development,
cellular senescence, innate immune responses and vascular
homeostasis. ASF1A, anti-silencing function 1A; ac, acetylation;
CAF-1, chromatin assembly factor 1; CBP, CREB-binding protein; DSB,
double-strand break; EndMT, endothelial-mesenchymal transition;
HIRA, histone regulator A; HR, homologous recombination; H3K18la,
histone H3 lysine 18 lactylation; H3K56ac, histone H3 lysine 56
acetylation; IPO4, importin 4; IRF3, interferon regulatory factor
3; MDC1, mediator of DNA damage checkpoint 1; Oct4, octamer-binding
transcription factor 4; RAD51, RAD51 recombinase; RIF1, replication
timing regulatory factor 1; ROS, reactive oxygen species; SAHF,
senescence-associated heterochromatic foci; TONSL, Tonsoku-like DNA
repair protein; 53BP1, p53 binding protein 1.

Figure 3

Mechanistic roles of ASF1A across
malignant and non-neoplastic disorders. Dysregulated ASF1A drives
leukemogenesis, tumor proliferation, EMT and therapeutic resistance
through distinct signaling axes in a tissue-specific manner, while
its perturbation in non-neoplastic contexts disrupts embryonic
development and promotes vascular pathology. ASF1A, anti-silencing
function 1A; Ac, acetylation; CRPC, castration-resistant prostate
cancer; EMT, epithelial-mesenchymal transition; EndMT,
endothelial-mesenchymal transition; H3K56ac, histone H3 lysine 56
acetylation; H3K18la, histone H3 lysine 18 lactylation; ICB, immune
checkpoint blockade; NHEJ, nonhomologous end-joining; PARPi, poly
(ADP-ribose) polymerase inhibitor; ZEB1, zinc finger E-box binding
homeobox 1.
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Copy and paste a formatted citation
Spandidos Publications style
Yin J, Zhuo X, Wen L, Wang X, Luo T and Wang Q: ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review). Exp Ther Med 32: 289, 2026.
APA
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., & Wang, Q. (2026). ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review). Experimental and Therapeutic Medicine, 32, 289. https://doi.org/10.3892/etm.2026.13284
MLA
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., Wang, Q."ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review)". Experimental and Therapeutic Medicine 32.4 (2026): 289.
Chicago
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., Wang, Q."ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review)". Experimental and Therapeutic Medicine 32, no. 4 (2026): 289. https://doi.org/10.3892/etm.2026.13284
Copy and paste a formatted citation
x
Spandidos Publications style
Yin J, Zhuo X, Wen L, Wang X, Luo T and Wang Q: ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review). Exp Ther Med 32: 289, 2026.
APA
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., & Wang, Q. (2026). ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review). Experimental and Therapeutic Medicine, 32, 289. https://doi.org/10.3892/etm.2026.13284
MLA
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., Wang, Q."ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review)". Experimental and Therapeutic Medicine 32.4 (2026): 289.
Chicago
Yin, J., Zhuo, X., Wen, L., Wang, X., Luo, T., Wang, Q."ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review)". Experimental and Therapeutic Medicine 32, no. 4 (2026): 289. https://doi.org/10.3892/etm.2026.13284
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