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. 2024 Jan 16:2024:10.17912/micropub.biology.001108.
doi: 10.17912/micropub.biology.001108. eCollection 2024.

YY1-dependent transcriptional regulation manifests at the morula stage

Mizuki Sakamoto  1 , Takashi Ishiuchi  1
Affiliations

YY1-dependent transcriptional regulation manifests at the morula stage

Mizuki Sakamoto et al. MicroPubl Biol. .

Abstract

YY1 plays multifaceted roles in various cell types. We recently reported that YY1 regulates nucleosome organization in early mouse embryos. However, despite the impaired nucleosome organization in the absence of YY1, the transcriptome was minimally affected in eight-cell embryos. We then hypothesized that YY1 might prepare a chromatin environment to regulate gene expression at later stages. To test this possibility, we performed a transcriptome analysis at the morula stage. We found that a substantial number of genes are aberrantly expressed in the absence of YY1. Furthermore, our analysis revealed that YY1 is required for the transcription of LINE-1 retrotransposons.

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Conflict of interest statement

The authors declare that there are no conflicts of interest present.

Figures

Figure 1. <b>YY1 regulates transcription at the morula stage.</b>
Figure 1. YY1 regulates transcription at the morula stage.
(A) Schematic illustration showing the experiments for Yy1 knockdown (KD). (B) (Left) Representative images of immunostaining for YY1 upon Yy1 KD. Morulae were used for immunostaining. Scale bar, 20 μm. (Right) Plots showing YY1 signal intensity in morulae. Each dot represents the nuclear YY1 signal intensity normalized by the signal intensity of DAPI. ***p < 0.001, Wilcoxon rank sum exact test. Data shown are mean ± s.e.m. n=12 (control KD), 11 ( Yy1 KD). (C) MA plots showing the changes in gene expression between control and Yy1 KD morulae. Differentially expressed genes were defined by FDR < 0.05. Upregulated (n = 460) and downregulated (n = 988) genes in Yy 1 KD embryos are colored in red and blue, respectively. (D) Motif analysis at the promoters of downregulated (left) and upregulated genes (right) upon Yy1 KD. The top three motifs are shown. (E) Venn diagrams showing the overlap of between the differentially expressed genes in Yy1 KD morulae and the genes proximal to YY1 binding sites. (F) Pile-up analysis of Hi-C data from eight-cell embryos. (Left two diagrams) Heatmaps showing interaction between YY1-binding sites and the promoters of differentially expressed genes in Yy1 KD morulae. (Right two diagrams) The same analysis was performed for the promoters of randomly selected or highly expressed non-differentially expressed genes. Genes located on the Y chromosome were excluded. (G) Venn diagrams showing the overlap of down- or up-regulated genes in YY1-depleted morulae and mESC. The results from two independent public RNA-seq datasets (Weintraub et al. 2017; Hsieh et al. 2022) are shown on the left and right, respectively. (H) Volcano plots showing the changes in the expression of repetitive elements upon Yy1 KD in morulae. Upregulated (n = 12) and downregulated (n = 12) repetitive elements in Yy 1 KD embryos are colored in red and blue, respectively. (I) Heatmaps showing the enrichment of RNA-seq reads at YY1-bound L1Md_T loci in control and Yy1 KD embryos at the eight-cell and morula stages. Multi-mapped reads were included for this analysis.
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Grants and funding

This work was supported by grants from MEXT Grant-in-Aid for Scientific Research on Innovative Areas (JP19H05756) (T.I.) and the Japan Science and Technology Agency (JST) Support for Pioneering Research Initiated by the Next Generation (SRPING; JPMJSP2133 to M.S.).

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