Abstract
Recently, there has been tremendous progress in characterizing the transcriptional network regulating human embryonic stem cells (hESCs; MacArthur etal., 2009; Loh etal., 2011), including those signaling events mediated by Oct4, Nanog, and Sox2. There is growing interest in the epigenetic machinery involved in hESC self-renewal and differentiation. In general, epigenetic regulation includes chromatin reorganization, DNA modification, and histone modification, which are not directly related to alterations in DNA sequences. Various protein complexes, including Polycomb, trithorax, nucleosome remodeling deacetylase, SWI/SNF, and Oct4, have been shown to play critical roles in epigenetic control of hESC physiology. Hence, we will formally review recent advances in unraveling the multifaceted role of epigenetic regulation in hESC self-renewal and induced differentiation, particularly with respect to chromatin remodeling and DNA methylation events. Elucidating the molecular mechanisms underlying the maintenance/differentiation of hESCs and reprogramming of somatic cells will greatly strengthen our capacity to generate various types of cells to treat human diseases.
Highlights
There has been tremendous progress in characterizing the transcriptional network regulating human embryonic stem cells, including those signaling events mediated by Oct4, Nanog, and Sox2
Since long-interspersed element (LINE), Alu and SVA repetitive elements are frequently located in proximity to genes with protein coding capacities (Cordaux and Batzer, 2009), these inhibitory effects will most likely spread to the adjacent genes, epigenetically regulating gene expression in human embryonic stem cells (hESCs)
In many human cancers, CpG hypomethylation has been observed in repetitive DNA elements, LINE, short-interspersed element (SINE), LTR, and satellite repeats (Rauch et al, 2008; Bollati et al, 2009; Choi et al, 2009; Igarashi et al, 2010; Xie et al, 2010), reflecting that tumorigenesis potentially shares some common epigenetic regulation pathways with hESC maintenance and somatic cell reprogramming
Summary
There has been tremendous progress in characterizing the transcriptional network regulating human embryonic stem cells (hESCs; MacArthur et al, 2009; Loh et al, 2011), including those signaling events mediated by Oct4, Nanog, and Sox2. Brg1 has been shown to interact with the key regulators of pluripotency, Oct4, Sox2, and NANOG, and exhibits a highly correlated genome-wide binding patterns with these proteins (Liang et al, 2008; Ho et al, 2009), suggesting a cooperative role of SWI/SNF complexes in keeping the cells in the undifferentiated state.
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