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论文题目: Human-Specific Hypomethylation of CENPJ, a Key Brain Size Regulator
作者: Shi L, Lin Q, Su B
联系作者: sub@mail.kiz.ac.cn
发表年度: 2016
DOI:
摘要: Both the enlarged brain and concurrent highly developed cognitive skills are often seen as distinctive characteristics that set humans apart from other primates. Despite this obvious differentiation, the genetic mechanisms that underlie such human-specific traits are not clearly understood. In particular, whether epigenetic regulations may play a key role in human brain evolution remain elusive. In this study, we used bisulfite sequencing to compare the methylation patterns of four known genes that regulate brain size (ASPM, CDK5RAP2, CENPJ, and MCPH1) in the prefrontal cortex among several primate species spanning the major lineages of primates (i.e., humans, great apes, lesser apes, and Old World monkeys). The results showed a human-specific hypomethylation in the 5' UTR of CENPJ in the brain, where methylation levels among humans are only about one-third of those found among nonhuman primates. Similar methylation patterns were also detected in liver, kidney, and heart tissues, although the between-species differences were much less pronounced than those in the brain. Further in vitro methylation assays indicated that the methylation status of the CENPJ promoter could influence its expression. We also detected a large difference in CENPJ expression in the human and nonhuman primate brains of both adult individuals and throughout the major stages of fetal brain development. The hypomethylation and comparatively high expression of CENPJ in the central nervous system of humans suggest that a human-specific-and likely heritable-epigenetic modification likely occurred during human evolution, potentially leading to a much larger neural progenitor pool during human brain development, which may have eventually contributed to the dramatically enlarged brain and highly developed cognitive abilities associated with humans.
刊物名称: Molecular Biology and Evolution
论文出处: http://mbe.oxfordjournals.org/content/31/3/594
影响因子: 13.649 (2015年)