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General Comment |
NCBI Summary:
This gene encodes a nuclear protein that is similar to the product of the Drosophila male-specific lethal-3 gene. The Drosophila protein plays a critical role in a dosage-compensation pathway, which equalizes X-linked gene expression in males and females. Thus, the human protein is thought to play a similar function in chromatin remodeling and transcriptional regulation, and it has been found as part of a complex that is responsible for histone H4 lysine-16 acetylation. This gene can undergo X inactivation. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 7 and 8. [provided by RefSeq, Jul 2010]
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Comment |
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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