更新于：2024-09-19

ASF1A

更新于：2024-09-19

基本信息

别名

anti-silencing function 1A histone chaperone、Anti-silencing function protein 1 homolog A、ASF1A

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简介

Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly (PubMed:10759893, PubMed:11897662, PubMed:12842904, PubMed:14718166, PubMed:15664198, PubMed:16151251, PubMed:21454524). Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly (PubMed:11897662, PubMed:14718166, PubMed:15664198). Promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks: acts by mediating histone replacement at DSBs, leading to recruitment of the MMS22L-TONSL complex and subsequent loading of RAD51 (PubMed:29478807). Also involved in the nuclear import of the histone H3-H4 dimer together with importin-4 (IPO4): specifically recognizes and binds newly synthesized histones with the monomethylation of H3 'Lys-9' and acetylation at 'Lys-14' (H3K9me1K14ac) marks, and diacetylation at 'Lys-5' and 'Lys-12' of H4 (H4K5K12ac) marks in the cytosol (PubMed:21454524, PubMed:29408485). Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit (PubMed:15621527).

关联

100 项与 ASF1A 相关的临床结果

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100 项与 ASF1A 相关的转化医学

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0 项与 ASF1A 相关的专利（医药）

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111

项与 ASF1A 相关的文献（医药）

2024-10-01·Reproductive Toxicology

Effects of Glycine on epigenetic modification and early embryonic development in porcine oocytes exposed to monobutyl phthalate

Article

作者: Li, Suo ; Gao, Lepeng ; Teng, Ran ; Zhang, Enbo ; Sun, Yutong ; Sun, Xiaoqing

Monobutyl phthalate (MBP) is the primary active metabolite of dibutyl phthalate (DBP), the key plasticizer component. A substantial body of evidence from studies conducted on both animals and humans indicates that MBP exposure could result in harmful impacts on toxicity pathways. In addition, it can seriously affect human and animal reproductive health. In our present study, we showed that exposure to MBP causes abnormal epigenetic modifications in porcine oocytes and failure of early embryonic development. However, glycine (Gly) can protect oocytes and early embryos from damage caused by MBP. Our study indicated a significant decrease in the percentage of porcine oocytes that reached the metaphase II (MII) phase when exposed to MBP. SET-domain-containing 2(SETD2)-mediated H3K36me3 histone methylation was detected, and the results showed that MBP significantly decreased the protein expression of H3K36me3 and SETD2. Moreover, the expression of the DNA break markers γH2AX and the mRNA expression of Asf1a, and Asf1b increased in the MBP group. The detection of DNA methylation marker proteins showed that MBP significantly increased the fluorescence intensity of 5-methylcytosine (5mC). The results from our RT-qPCR analysis demonstrated a significant decrease in the mRNA expression of the DNA methylation-related genes Dnmt1 and Dnmt3a, as well as the embryonic developmental potential-related genes Oct4 and Nanog, in porcine oocytes following exposure to MBP. Additionally, the mRNA expression of p53 significantly increased. Subsequently, the effects of MBP on early embryonic development were examined via parthenogenesis activation (PA) and in vitro fertilization (IVF). Exposure to MBP significantly impacted the development of embryos in both PA and IVF processes. The TUNEL staining data showed that MBP significantly increased embryonic apoptosis. However, Gly can ameliorate MBP-induced defects in oocyte epigenetic modifications and early embryonic development.

2024-10-01·Biochemical and Biophysical Research Communications

Structural insights into instability of the nucleosome driven by histone variant H3T

Article

作者: Liu, Yongrui ; Yang, Yang ; Xu, Li ; Hu, Shenglin

The testis-specific histone variant H3T plays a crucial role in chromatin reorganization during spermatogenesis by destabilizing nucleosomes. However, the structure basis for the nucleosome instability driven by H3T is not fully understand. In this study, we determinate the crystal structure of H3T-H4 in complex with histone chaperone ASF1a at 2.8 Å resolution. Our findings reveal that H3T-H4 binds ASF1a similarly to the conventional H3.1-H4 complex. However, significant structural differences are observed in the H3 α1 helix, the N- and C-terminal region of α2, and N-terminal region of L2. These differences are driven by H3T-specific residues, particularly Val111. Unlike the smaller Ala111 in H3.1, we find that bulkier residue Val111 fits well within the ASF1-H3T-H4 complex, but is difficult to arrange in nucleosome structure. Given that H3.1-Ala111/H3T-Val111 is located at the DNA binding and tetramerization interface of H3-H4, it is likely that Ala111Val substitution will lead to the instability of the corresponding area in nucleosome, contributing to instability of H3T-containing nucleosome. These structural findings may elucidate the role of H3T in chromatin reorganization during spermatogenesis.

2024-09-01·Journal of Biological Chemistry

HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding

Article

作者: Gardner, Lauren ; Szurgot, Mary ; Marmorstein, Ronen ; Schultz, David C ; Vogt, Austin

The HIRA histone chaperone complex is comprised of four protein subunits: HIRA, UBN1, CABIN1, and transiently associated ASF1a. All four subunits have been demonstrated to play a role in deposition of the histone variant H3.3 onto areas of actively transcribed euchromatin in cells. The mechanism by which these subunits function together to drive histone deposition has remained poorly understood. Here we present biochemical and biophysical data supporting a model whereby ASF1a delivers histone H3.3/H4 dimers to the HIRA complex, H3.3/H4 tetramerization drives the association of two HIRA/UBN1 complexes, and the affinity of the histones for DNA drives release of ASF1a and subsequent histone deposition. These findings have implications for understanding how other histone chaperone complexes may mediate histone deposition.