NCBI Summary:
This gene encodes a member of the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 gene in yeast. The protein is a key component of a histone donor complex that functions in nucleosome assembly. It interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. [provided by RefSeq, Jul 2008]
General function
, Epigenetic modifications
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Cellular localization
Nuclear
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Ovarian function
Early embryo development
, Pluripotent cell derivation
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Anti-silencing Factor 1A is Associated with Genome Stability Maintenance of Mouse Preimplantation Embryos†. Deng K et al. (2020) Genome stability is critical for the normal development of preimplantation embryos, as DNA damages may result in mutation and even embryo lethality. Anti-silencing factor 1A (ASF1A) is a histone chaperone and enriched in the MII oocytes as a maternal factor, which may be associated with the maintenance of genome stability. Thus, this study was undertaken to explore the role of ASF1A in maintaining the genome stability of early mouse embryos. The ASF1A expressed in the preimplantation embryos and displayed a dynamic pattern throughout the early embryonic development. Inhibition of ASF1A expression decreased embryonic development and increased DNA damages. Overexpression of ASF1A improved the developmental potential and decreased DNA damages. When 293 T cells that had been integrated with RGS-NHEJ were co-transfected with plasmids of pcDNA3.1-ASF1A, gRNA-NHEJ and hCas9, less cells expressed eGFP, indicating that non-homologous end joining (NHEJ) was reduced by ASF1A. When 293 T cells were co-transfected with plasmids of HR-donor, gRNA-HR, hCas9 and pcDNA3.1-ASF1A, more cells expressed eGFP, indicating that homologous recombination (HR) was enhanced by ASF1A. These results indicate that ASF1A may be associated with the genome stability maintenance of early mouse embryos and this action may be mediated by promoting DNA damage repair through HR pathway.//////////////////
Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming. Gonzalez-Mu?E 2014 et al.
Unfertilized oocytes have the intrinsic capacity to remodel sperm and the nuclei of somatic cells. The discoveries that cells can change their phenotype from differentiated to embryonic state using oocytes or specific transcription factors have been recognized as two major breakthroughs in the biomedical field. Here, we show that ASF1A, a histone-remodeling chaperone specifically enriched in the metaphase II human oocyte, is necessary for reprogramming of human adult dermal fibroblasts (hADFs) into undifferentiated iPSCs. We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells. Our report underscores the importance of studying the unfertilized MII oocyte as a means to understand the molecular pathways governing somatic cell reprogramming.
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Expression regulated by
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Ovarian localization
Oocyte
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Identifying candidate oocyte reprogramming factors using cross-species global transcriptional analysis. Awe JP 2013 et al.
There is mounting evidence to suggest that the epigenetic reprogramming capacity of the oocyte is superior to that of the current factor-based reprogramming approaches and that some factor-reprogrammed induced pluripotent stem cells (iPSCs) retain a degree of epigenetic memory that can influence differentiation capacity and may be linked to the observed expression of immunogenicity genes in iPSC derivatives. One hypothesis for this differential reprogramming capacity is the 'chromatin loosening/enhanced reprogramming' concept, as previously described by John Gurdon and Ian Wilmut, as well as others, which postulates that the oocyte possesses factors that loosen the somatic cell chromatin structure, providing the epigenetic and transcriptional regulatory factors more ready access to repressed genes and thereby significantly increasing epigenetic reprogramming. However, to empirically test this hypothesis a list of candidate oocyte reprogramming factors (CORFs) must be ascertained that are significantly expressed in metaphase II oocytes. Previous studies have focused on intraspecies or cross-species transcriptional analysis of up to two different species of oocytes. In this study, we have identified eight CORFs (ARID2, ASF1A, ASF1B, DPPA3, ING3, MSL3, H1FOO, and KDM6B) based on unbiased global transcriptional analysis of oocytes from three different species (human, rhesus monkey, and mouse) that both demonstrate significant (p<0.05, FC>3) expression in oocytes of all three species and have well-established roles in loosening/opening up chromatin structure. We also identified an additional 15 CORFs that fit within our proposed 'chromatin opening/fate transformative' (COFT) model. These CORFs may be able to augment Shinya Yamanaka's previously identified reprogramming factors (OCT4, SOX2, KLF4, and cMYC) and potentially facilitate the removal of epigenetic memory in iPSCs and/or reduce the expression of immunogenicity genes in iPSC derivatives, and may have applications in future personalized pluripotent stem cell based therapeutics.
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