Fetal chromosomal aneuploidies can lead to fetal loss and major birth defects.The best known chromosomal aneuploidy is Down syndrome,or medically termed trisomy 21,where the affected individual has an extra full or pa...Fetal chromosomal aneuploidies can lead to fetal loss and major birth defects.The best known chromosomal aneuploidy is Down syndrome,or medically termed trisomy 21,where the affected individual has an extra full or partial copy of chromosome 21.The extra copy of genetic material is the culprit for causing developmental problem for affected individuals.Three types of Down syndrome exist:trisomy 21 accounts for 95%of cases,translocation accounts for about 4%and mosaicism accounts for about 1%.Less common chromosomal aneuploidies include Edward syndrome(trisomy 18),Patau syndrome(trisomy 13),Turner syndrome(45,X),Klinefelter syndrome(47,XXY),and 47,展开更多
Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA ...Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.展开更多
文摘Fetal chromosomal aneuploidies can lead to fetal loss and major birth defects.The best known chromosomal aneuploidy is Down syndrome,or medically termed trisomy 21,where the affected individual has an extra full or partial copy of chromosome 21.The extra copy of genetic material is the culprit for causing developmental problem for affected individuals.Three types of Down syndrome exist:trisomy 21 accounts for 95%of cases,translocation accounts for about 4%and mosaicism accounts for about 1%.Less common chromosomal aneuploidies include Edward syndrome(trisomy 18),Patau syndrome(trisomy 13),Turner syndrome(45,X),Klinefelter syndrome(47,XXY),and 47,
文摘Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.
