Cell: Scientists in China have revealed many human-specific chromosomal structural changes during development

February 4, 2021 /--- In a new study, Professor Su Bing, a researcher at the Kunming Institute of Zoology of the Chinese Academy of Sciences, Cheng Li, a researcher at Peking University's School of Life Sciences, and Shihua Zhang, a researcher at the Institute of Mathematics and Systems Science of the Chinese Academy of Sciences, reported on the 3D genome of the primate brain, by far the highest resolution, and demonstrated the molecular mechanisms of human brain evolution through cross-species multi-group analysis and experimental verification.
study was published online January 27, 2021 in the journal Cell under the title "3D Genome of macaque fetal brain reveals evolutionary innovations when primate corticogenesis."
from Cell, 2021, doi:10.1016/j.cell.2021.01.001.
patterns of human brain development stem from genetic changes accumulated during human evolution.
only a small number of different genetic changes have important functions.
challenge is to identify causal changes and their regulatory mechanisms that lead to unique patterns of brain development in humans.
monkeys are genetically similar to humans and are ideal models for studying the origin and development mechanisms of the human brain.
the genomes of mammalian species, including humans, are about two meters long and are compressed into nuclei of cells only 10 microns in diameter.
non-random compression is characterized by a three-dimensional distribution of tissues, which is very important for cell proliferation and differentiation during development.
recently, the invention of genome-wide chromosomal structure capture technology (Hi-C) provides a good opportunity to dissect the fine structure of the genome during brain development.
the new study, the researchers worked together across disciplines to analyze the brain's three-dimensional genome across species.
first used Hi-C technology to build a high-resolution 3D chromatin structure of the fetal brain of macaques.
the Hi-C map, which has a resolution of 1.5 kb and represents the highest resolution of the primate brain to date, has become a useful histological data set that reveals details of the structure of the 3D genome.
, they also generated transcriptional group diagrams, chromatin open area maps, and anchor protein CCCTC binding factor (CTCF) diagrams.
Based on these multi-group data, the researchers first built a fine map of the chromatin structure of the fetal brain of macaques and identified chromatin structures at different scales, including chromatin cells, topologically related domains (TADs), and chromatin rings.
they also found regulatory elements in the genome, such as enhancers.
then, using published human and mouse brain Hi-C data, they compared many human-specific chromatin structure changes, including 499 human-specific TAD and 1,266 human-specific chromatin rings.
noteworthy that these human-specific chromatin rings have been shown to be rich in enhancer-enhancer interactions, representing the origin of the brain development fine-tuning mechanism during human evolution.
Based on analysis of single-cell transcription group data on human brain development, the researchers observed that these human-specific chromatin-ring-related genes are highly expressed in the subplate lamina, a transient region of brain development that is critical to the formation and plasticity of neural circuits.
study found that the lower layers of the human plate showed extra-toothed expansion, about four times the thickness of the cortical plate, compared to macaques and mice.
the lower layers of the plate begin to decrease and eventually disappear after birth, little is known about this transient area.
findings provide the first evidence of the crucial role of the lower plates in forming human-specific brain structures during development.
In addition, the researchers found that many human-specific mutations, such as point mutations and structural changes, are located at the TAD boundary and chromatin ring anchoring regions, which may be the origin of the new binding site of transcription factors and the structure of human-specific chromatin.
they studied an example involving the EPHA7 gene, which is highly expressed in the lower plate and is critical for neuron tree bursts.
-specific point mutations known as EPHA7 lead to the formation of human-specific enhancers and chromatin rings.
by conducting experiments involving enhancer knockout in cell line, they have demonstrated that human-specific EPHA7 enhancer can cause regulatory changes in EPHA7 expression, affecting the development of degenerative degeneration.
new understanding of the genetic mechanisms of the origin of the human brain and is a valuable resource for the three-dimensional brain genome.
(Bioon.com) Reference: 1. Xin Luo et al.3D Genome of macaque fetal brain reveals evolution innovationarys when primate corticogenesis. Cell, 2021, doi:10.1016/j.cell.2021.01.001.2.3-D genome brain study uncovers human-specific regulatory changes during development