Abstract
Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here, we report on LiCAT-seq, a technique that enables simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells, and map the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions. Integrative analyses between the two datasets reveals strong association between the establishment of accessible chromatin and embryonic genome activation (EGA), and uncovers transcription factors and endogenous retrovirus (ERVs) specific to EGA. In particular, a large proportion of the early activated genes and ERVs are bound by DUX4 and become accessible as early as the 2- to 4-cell stages. Our results thus offer mechanistic insights into the molecular events inherent to human pre-implantation development.
Highlights
Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity
LiCAT-seq-generated CA data showing a high enrichment of reads around transcription start site (TSS) regions—and the correlations between profiles generated from 10 cells and bulk cells were high (Supplementary Figure 1a, b)
When promoters were categorized based upon high, intermediate and low-CpG content (high-CpG-density promoters (HCPs), intermediate-CpG-density promoters (ICPs), and low-CpG-density promoters (LCPs)), we observed a stronger enrichment of CA reads at promoters with a higher GC ratio, which is similar to the enrichment of histone H3 lysine 4 trimethylation (H3K4me3)[15], suggesting a potential synergistic function of CA and H3K4me[3] (Supplementary Figure 1c)
Summary
Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. We develop LiCAT-seq (low-input chromatin accessibility (CA) and transcriptome sequencing), a technique that enables the simultaneous assay of CA and gene expression (GE) with low-input samples (Fig. 1a) We apply this technique to profiling chromatin structure and GE dynamics during human pre-implantation embryos and demonstrate the key regulatory dynamics for genes activated during embryonic genome activation (EGA). We find that a large proportion of the early activated genes and endogenous retrovirus (ERV) elements possess DUX4-binding sites and become accessible as early as the 2- to 4-cell stages In one such example, we observe widespread DUX4 binding on MLT2A1, which flanks HERVL, a subfamily of ERV that become accessible during major EGA. Our work suggests the important roles of early TFs in the remodeling of the closed chromatin during human pre-implantation embryo development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
