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Changes in genome topology accompany cell reprogramming
Overexpression of reprogramming factors drives somatic cells to become induced pluripotent stem cells (iPSCs). Although iPSCs are able to contribute to all tissues, there is evidence that the differentiation propensity of iPSCs reflects their tissue of origin.
To understand whether the 3D genome structure contributes to differentiation bias of in iPSCs, a team led by Thomas Graf from Pompeu Fabra University in Barcelona sought to understand how genome topology changes during reprogramming of somatic cells. They found the following:
Taken together, these data show that changes in genome topology accompany cell reprogramming. Established pluripotent cells share the same topology regardless of their cell of origin, although early passage cells have some differences.
Read the full paper in Cell Stem Cell, March 2016.
Role of N6-methyladenine in epigenetic silencing
DNA methylation is commonly thought to occur in mammals solely as 5-methylcytosine. Although existence of N6-methyladenine (N6-mA) in organisms such as insects, nematodes and green algae – where it has a gene activating role – its presence has not previously been confirmed in mammals.
A team led by Andrew Xiao from Yale School of Medicine, Connecticut have uncovered evidence of N6-adenine modification in mammals. They found the following:
These results demonstrate that N6-mA has a role in epigenetic silencing in mammals, distinct from its gene activating role in other organisms.
Read the full paper in Nature, March 2016.
Cell fate determination begins the four-cell stage
Segregation of the trophectoderm (TE) and inner cell mass (ICM) occurs primarily as a result of asymmetric cell divisions in the pre-implantation embryo. However, it is still unknown when cells start to differ from each other in mammalian development, and whether the initial differences are important for subsequent cell fate.
To understand how and when embryonic and extra-embryonic cell fates are established, a team led by Magdalena Zernicka-Goetz from the University of Cambridge, UK characterized individual cell transcriptomes during pre-implantation development. Here is what they found:
These results indicate that cell fate is determined by heterogeneous expression of pluripotency factors from as early as the four-cell stage.
Read the full paper in Cell, March 2016.
Sox2 DNA-binding properties predict mammalian cell fate
Transcription factors Oct4 and Sox2 are involved in the pluripotent cell lineage in the early mammalian embryo. However, as most cells express these transcription factors, it remains unknown how only some cells acquire a pluripotent state.
To understand how transcription factor-DNA interactions change during cell fate determination in vivo, a team led by Nicolas Plachta from the Agency for Science, Technology and Research in Singapore investigated the DNA-bindnig dynamics of Oct4 and Sox2 in the developing mouse embryo. The found the following:
The results in this paper demonstrate that Sox2 DNA-binding properties predict mammalian cell fate at teh four-cell stage. The authors show that Sox2 DNA binding properties are driven by epigenetic changes.
Read the full paper in Cell, March 2016.
UTX is a coactivator of the TAL-1 transcriptional regulatory program
The role of sperm in embryonic gene expression
The epigenetic state of the sperm nucleus has been suggested to influence transcription in the embryo. However, this hypothesis has recently been questioned.
By comparing the development of sperm and spermatid-derived frog embryos, a team led by Jerome Jullien from the University of Cambridge, UK investigated the role of sperm in embryonic development. They found the following:
The results in the paper show that correct gene programming of paternal chromatin relies on effective H3K27me3-mediated repression at the spermatid to sperm transition.
Read the full paper in Genome Research, March 2016.