Transcriptional control of human embryo genome activation

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Juha Kere from Karolinska Institute and King's College London.

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Date: Wednesday, April 11, 2018

Time: 13:30-14:30

Venue: D015, Level D, Lab 1

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Speaker:

Dr. Juha Kere, Karolinska Institute and King's College London

Title:
Transcriptional control of human embryo genome activation

Abstract:

After fertilization of the egg cell, the embryonal development starts with its individual transcriptome activation (Embryo Genome Activation, EGA) accompanied by the degradation of maternal transcripts, to be followed later with new waves of transcriptional activation. Single-cell transcriptome analysis can unveil these steps in detail, but pose also challenges, such as ≈30-fold changes in total cellular mRNA content. To understand human EGA, we performed single-cell transcriptome sequencing of over 340 cells, including oocytes, zyogtes and single blastomeres from 4-cell and 8-cell embryos, obtained by informed consent as donations after in vitro fertilization treatments¹. The total content of mRNA molecules remained essentially unchanged between oocytes and zygotes, but revealed an increase of DUX4 repeat-sequence transcripts². Comparison of the transcriptomes of oocytes and 4-cell stage blastomeres identified the first 32 embryonally transcribed genes, including previously uncharacterized Paired-like (PRDL) homeobox domain genes, as well as the significant reduction of thousands of maternal transcripts¹. At the 8-cell stage, 129 additional genes were upregulated compared to the 4-cell stage. Our transcription start site targeted data allowed also the identification of critical regulators of EGA as 36 bp and 35 bp conserved promoter elements at the two stages of EGA, respectively. We cloned and confirmed the genomic structures of seven new PRDL genes expressed only during EGA. Their functional analysis confirmed their roles as transcriptional regulators, ranging from LEUTX as a strong transcriptional activator to DPRX with a strong downregulatory profile³. These data constitute a resource for understanding the earliest steps of human embryonal development and provide new genes of interest for study of pluripotency and cell technologies, such as iPS cell reprogramming by CRISPRa technology⁴.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit