Regulation of Polycomb Repression by O-GlcNAcylation: Linking Nutrition to Epigenetic Reprogramming in Embryonic Development and Cancer

Histone acetylation plays an important role in the chromatin structure prior to zygotic gene expression during early embryonic development. Successful animal clones indicate that differentiated somatic nuclei must be reprogrammed to some extent during pre-implantation development. However, the molecular mechanisms regarding epigenetic reprogramming of somatic nuclei in the early-stage embryos are poorly understood. To test this, the patterns of hyperacetylated histone H4 lysine 5 (AcH4K5) in the nuclear-transferred (NT) embryos were monitored, comparing in vitro fertilized (IVF) embryos and Trichostatin A (TSA)-NT embryos with TSA-treated cells. The intensity signals of AcH4K5 were observed in early-stage embryos and somatic cells (bovine ear skin fibroblasts composed of about 80% at G0/G1 stage) by immunofluorescence analysis with anti-AcH4K5 using image the analyzer system, SigmaScan-pro V5.01 (SPSS, Inc., Chicago, IL, USA). Our data were analyzed by analysis of variance (ANOVA) using an SAS package (SAS Institute, Inc., Cary, NC, USA). Somatic cells were exposed to TSA (1 μM for 60 h), a specific inhibitor of histone deacetylase (HDAC), to induce hyperacetylation prior to somatic cell nuclear transfer. Signal intensity for AcH4K5 in TSA-treated cells (n = 80) was significantly increased (P < 0.05), which was approximately double compared to that of normal cells (n = 80). In normal cells, histone H4 acetylation was profoundly reduced from the pro-metaphase to the early telophase and then reappeared at the late telophase. Acetylation signals of TSA-treated cells gradually increased to the early anaphase, abruptly decreased at the late anaphase and the early telophase, and recovered during late telophase. During early embryonic development (1 cell to 8 cell stage), NT embryos (n = 8) were hypoacetylated at the metaphase, whereas IVF (n = 10) and TSA-NT embryos (n = 8) were hyperacetylated. Our findings demonstrate that aberrant epigenetic reprogramming of histone modification occurs as early as the pronuclear stage in cloned embryos.

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Progressive domain segregation in early embryonic development and underlying correlation to genetic and epigenetic changes

10.1101/2021.02.02.429282 ◽

2021 ◽

Author(s):

Hui Quan ◽

Hao Tian ◽

Sirui Liu ◽

Yue Xue ◽

Yu Zhang ◽

...

Keyword(s):

Embryonic Development ◽

Chromatin Structure ◽

Epigenetic Reprogramming ◽

Epigenetic Changes ◽

Sequence Dependence ◽

Germ Layers ◽

Related Function ◽

Chromatin Structural ◽

Mixed Prairie ◽

Genome Activation

AbstractChromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming and the corresponding sequence dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests and prairies, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which notable domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. Chromatin of ectoderm shows the weakest and endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges in further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest DNA sequence as a possible driving force for the establishment of chromatin 3D structures which affect profoundly the expression profile. Other possible factors correlated with/influencing chromatin structures, including temperature, germ layers, and cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.

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Progressive Domain Segregation in Early Embryonic Development and Underlying Correlation to Genetic and Epigenetic Changes

Cells ◽

10.3390/cells10102521 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2521

Author(s):

Hui Quan ◽

Hao Tian ◽

Sirui Liu ◽

Yue Xue ◽

Yu Zhang ◽

...

Keyword(s):

Embryonic Development ◽

Chromatin Structure ◽

Epigenetic Reprogramming ◽

Epigenetic Changes ◽

Sequence Dependence ◽

Germ Layers ◽

Related Function ◽

Chromatin Structural ◽

Mixed Prairie ◽

Genome Activation

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.

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Phase separation during mouse early embryonic development and underlying genetic and epigenetic correlations

10.1101/521401 ◽

2019 ◽

Cited By ~ 2

Author(s):

Hui Quan ◽

Sirui Liu ◽

Yu Zhang ◽

Wei Xie ◽

Yi Qin Gao

Keyword(s):

Structural Change ◽

Embryonic Development ◽

Epigenetic Reprogramming ◽

Sequence Dependence ◽

Temperature Changes ◽

Functional Realization ◽

Chromatin Structural ◽

Two Stages ◽

The Relationship ◽

Specific Phase

ABSTRACTChromatin undergoes drastic organization and epigenetic reprogramming during embryonic development in mammals. However, the relationship among global structural change, epigenetic reprogramming, and functional implementation is largely unknown. Based on the analysis of latest published Hi-C data of post-implantation stages, we present a consistent view of the chromatin structural change and the corresponding sequence dependence. Two types of sequentially, genetically and transcriptionally distinct domains, forests and prairies, show systematic and overall increase of spatial segregation during embryonic development, but with notable mixing occurring at two stages, ZGA and implantation. The segregation level change largely coincides with the change of genetic and epigenetic properties. Detailed gene functions in specific phase-changing domains during implantation were analyzed, based on which a possible mechanism of functional realization during implantation was proposed. Interestingly, body temperature changes coincide with the change in chromatin segregation, implying that temperature is a possible factor influencing global chromatin structure.

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Live Confocal Analysis of Fertilization and Early Development

Microscopy and Microanalysis ◽

10.1017/s1431927600031135 ◽

2001 ◽

Vol 7 (S2) ◽

pp. 1012-1013

Author(s):

Uyen Tram ◽

William Sullivan

Keyword(s):

Drosophila Melanogaster ◽

Embryonic Development ◽

Real Time ◽

Early Development ◽

Fluorescent Probes ◽

Primary Defect ◽

Fluorescent Analysis ◽

Dynamic Event ◽

Enormous Amount ◽

Fluorescent Studies

Embryonic development is a dynamic event and is best studied in live animals in real time. Much of our knowledge of the early events of embryogenesis, however, comes from immunofluourescent analysis of fixed embryos. While these studies provide an enormous amount of information about the organization of different structures during development, they can give only a static glimpse of a very dynamic event. More recently real-time fluorescent studies of living embryos have become much more routine and have given new insights to how different structures and organelles (chromosomes, centrosomes, cytoskeleton, etc.) are coordinately regulated. This is in large part due to the development of commercially available fluorescent probes, GFP technology, and newly developed sensitive fluorescent microscopes. For example, live confocal fluorescent analysis proved essential in determining the primary defect in mutations that disrupt early nuclear divisions in Drosophila melanogaster. For organisms in which GPF transgenics is not available, fluorescent probes that label DNA, microtubules, and actin are available for microinjection.

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