Abstract
A major event in embryonic development is the rearrangement of epigenetic information as the somatic genome is reprogrammed for a new round of organismal development. Epigenetic data are held in chemical modifications on DNA and histones, and there are dramatic and dynamic changes in these marks during embryogenesis. However, the mechanisms behind this intricate process and how it is regulating and responding to embryonic development remain unclear. As embryos develop from totipotency to pluripotency, they pass through several distinct stages that can be captured permanently or transiently in vitro. Pluripotent naïve cells resemble the early epiblast, primed cells resemble the late epiblast, and blastomere-like cells have been isolated, although fully totipotent cells remain elusive. Experiments using these in vitro model systems have led to insights into chromatin changes in embryonic development, which has informed exploration of pre-implantation embryos. Intriguingly, human and mouse cells rely on different signaling and epigenetic pathways, and it remains a mystery why this variation exists. In this review, we will summarize the chromatin rearrangements in early embryonic development, drawing from genomic data from in vitro cell lines, and human and mouse embryos.
Highlights
Each cell contains the same DNA that is interpreted to provide specialized cell function, yet the interpretation of the DNA code is cell type-specific, and epigenetic barriers exist that impair and permit cell type conversions
A/B compartments were unaffected, but topologically associated domains (TADs) and chromatin loops were disrupted; once again, the effect on the mouse embryonic stem cells (mESCs) phenotype was modest, there was a proliferation defect if CTCF loss persisted (Nora et al, 2017). These results suggest that 3D structure is relatively uncoupled from cell type control, the precise 3D structure of embryonic cells has not been fully recapitulated in mESCs and remains inconclusive
An analysis of naïve and primed human ESCs (hESCs) states revealed that naïve cells express nicotinamide N-methyltransferase (NNMT) at high levels (Sperber et al, 2015), which is responsible for metabolizing S-adenosylmethionine (SAM), the major chemical donor for histone methyltransferases
Summary
Each cell contains the same DNA that is interpreted to provide specialized cell function, yet the interpretation of the DNA code is cell type-specific, and epigenetic barriers exist that impair and permit cell type conversions. The mechanism involves ZFP281 co-binding with EHMT1 to methylate H3K9 and inhibit genes in the early stages of mESC to EpiSC conversion (Mayer et al, 2020), while in the reverse case ZFP281 binds the NuRD co-repressor complex to suppress Nanog expression and enable exit from pluripotency (Fidalgo et al, 2012).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
