Received: 25 June 2018
|
Accepted: 17 August 2018
DOI: 10.1002/jcp.27386
ORIGINAL RESEARCH ARTICLE
Dynamics changes in the transcription factors during early
human embryonic development
Rasoul Godini | Hossein Fallahi
Department of Biology, School of Sciences,
Razi University, Kermanshah, Iran
Correspondence
Hossein Fallahi, Department of Biology,
School of Sciences, Razi University,
Baq‐e‐Abrisham, Kermanshah 6714414676,
Iran.
Email: h.fallahi@razi.ac.ir;
Fallahi.hossein@gmail.com
Abstract
Development of an embryo from a single cell, zygote, to multicellular morulae
requires activation of hundreds of genes that were mostly inactivated before
fertilization. Inevitably, transcription factors (TFs) would be involved in modulating
the drastic changes in gene expression pattern observed at all preimplantation stages.
Despite many ongoing efforts to uncover the role of TFs at the early stages of
embryogenesis, still many unanswered questions remained that need to be explored.
This could be done by studying the expression pattern of multiple genes obtained by
high‐throughput techniques. In the current study, we have identified a set of TFs that
are involved in the progression of the zygote to blastocyst. Global gene expression
patterns of consecutive stages were compared and differences documented.
Expectedly, at the early stages of development, only a few sets of TFs differentially
expressed while at the later stages hundreds of TFs appear to be upregulated.
Interestingly, the expression levels of many TFs show an oscillation pattern during
development indicating a need for their precise expression. A significant shift in gene
expression was observed during the transition from four‐ to eight‐cell stages, an
indication of zygote genome activation. Additionally, we have found 11 TFs that were
common in all stages including ATF3, EN1, IFI16, IKZF3, KLF3, NPAS3, NR2F2,
RUNX1, SOX2, ZBTB20, and ZSCAN4. However, their expression patterns did not
follow similar trends in the steps studied. Besides, our findings showed that both
upregulation and active downregulation of the TFs expression is required for
successful embryogenesis. Furthermore, our detailed network analysis identified the
hub TFs for each transition. We found that HNF4A, FOXA2, and EP300 are the three
most important elements for the first division of zygote.
KEYWORDS
embryogenesis, hub genes, network analysis, two‐cell stage, zygote genome activation
1 | INTRODUCTION
Molecular mechanism governing the embryos preimplantation stages
might hold the key to successful assisted reproductive technology
(Niakan, Han, Pedersen, Simon, & Pera, 2012). Early stages in
mammalian embryos harbor transcriptional activities that are
different from those observed in later stages of development. Shortly
after fertilization, the genomes should be reactivated (both maternal
and paternal genomes), a process that is known as zygote genome
activation (ZGA; M. T. Lee, Bonneau, & Giraldez, 2014; Tadros &
Lipshitz, 2009). The early stages of embryogenesis and proper
activation of the genome is crucial for successful development.
Previous studies have identified distinct, but overlapping
gene expression dynamics during the first stages of embryonic
J Cell Physiol. 2018;1–14. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1