htmlOn September 14, the sub-publication of " Cell " (Cell ) published online. , School of Animal Science and Technology, China Agricultural University, , a young top talent, Professor An Lei, a professor entitled "A small proportion of X-linked genes mediated transcriptional activation of small amounts of X-linked genes contribute to X chromosome upregulation in early embryos via BRD4-mediated transcriptional The research paper of activation revealed a new mechanism in which early embryo X chromosome is upregulated gene expression, thereby balancing sex chromosomes with autosome doses, and confirms its importance to early embryo development ability.
paper information
chromosomal dose balance is the prerequisite for maintaining genomic homeostasis and ensuring cell survival and normal growth. In mammals, females have 2 X chromosomes, while males have 1 X chromosome. The number and structural differences in the number and structure of the X and Y chromosome will lead to an imbalance between male and female gene dose and between sex chromosome and autosomals, destroying genomic homeostasis. However, during the evolutionary process, mammals have established two important chromosome dose balance mechanisms to maintain genomic homeostasis, including: females achieve dose balance between the sex chromosome and male sex chromosome by inactivating one X chromosome, i.e. X-chromosome inactivation (XCI); at the same time, both females and males, active X chromosomes further achieve dose balance between the sex chromosome and autosome through transcriptional upregulation, i.e. X-chromosome upregulation (XCU). These two chromosomal dose balance mechanisms are crucial for maintaining genomic homeostasis. In the past few decades, research on XCI has been very systematic and in-depth, and the understanding of relevant mechanisms has become increasingly complete. However, related research on XCU is very limited, especially in early development, the characteristics, mechanisms and developmental functions of XCU are unknown.
Previous related studies in XCU have always lacked appropriate algorithms to measure the gene compensation dose between chromosomes and the contribution of X chromosome linkage genes to chromosome dose. The team has established a special algorithm to measure the dynamic characteristics of X chromosome dose compensation based on the dynamic changes of each chromosome transcriptome in early embryos. Through in-depth analysis of early embryo transcriptome data, it was first found that XCU was initiated and occurred with the progress of zygotic genome activation (ZGA), and XCU and XCI coordinated to control the expression dose of X chromosomes in female embryos, which showed strong conservatism between mice and bovine. Surprisingly, a small number of genes (about 4%) on the X chromosome contributed a large proportion of XCU dose compensation, which is in sharp contrast to the XCI that occurs throughout X chromatin. More importantly, this study revealed that BRD4 plays an important role in initiating preimplantation embryos. The loss of BRD4 will lead to insufficient XCU, which will interfere with the mitochondrial function of blastocyst and damage the embryonic development potential. Furthermore, the team also found that XCU disorder caused by abnormal expression of BRD4 is closely related to the occurrence of diseases such as cholangiocarcinoma , indicating that this mechanism is of great significance for the maintenance of early embryonic and adult cell genome homeostasis.
chromosomal dose balance mechanisms in early embryos are very sensitive to the developmental environment. Previously, Professor Tian Jianhui's team was the first to reveal the mechanism of the lack of retinoic acid in the in vitro fertilization (IVF) culture environment, which causes insufficient XCI of IVF embryos, which in turn causes female embryo death and ultimately leads to gender imbalance in IVF birth. This work has attracted widespread attention in relevant fields at home and abroad, and has provided important ideas for the correction of the errors in the epitomization of IVF embryos in animal embryo production and human assisted reproduction and the improvement of the IVF culture system. In this study, the disclosure of early embryonic XCU occurrence patterns and regulatory mechanisms not only fills the important gap in the chromosomal dose balance mechanism in the field of development, but also provides an important reference for the improvement of the IVF development system and the treatment of related diseases in the future.
The young top talent from Professor Tian Jianhui's team of the School of Animal Science and Technology of China Agricultural University is the corresponding author of the paper , and the team's doctoral students Lu Qingji and Yang Qianying are the co-first authors of the paper. The research was funded by the National Key R&D Program Project (2021YFD1300901, 2017YFD0501901, 2017YFD0501905), the National Natural Science Foundation of Key Project (31930103), the special fund for basic scientific research business expenses of central universities (2022TC019), and the Beijing Innovation Team of the Livestock Industry Technology System (BAIC05-2022).
Original link: https://www.cell.com/current-biology/fulltext/S0960-9822(22)01381-1
Submitted by: College of Animal Science and Technology
Submitted by: College of Animal Science and Technology
Submitted by: College of Animal Science and Technology
Editor: Meng Xiangci
Editor: Yu Zhe
