Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking gen...Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking genomic DNA sequences of 41 TF genes involved in neuronal development.The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich（GC content60%）promoter with a CpG island.The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence（FGS）;however,more than half（37 of 70）of the GC-rich promoters were located in the proximal region between nucleotides—1 and—500.Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity.This study suggests a potential general mechanism for regulation of TF expression.展开更多
Vertebrate genomes are characterized with CpG deficiency, particularly for GCpoor regions. The GC content-related CpG deficiency is probably caused by context-dependent deamination of methylated CpG sites. This hypoth...Vertebrate genomes are characterized with CpG deficiency, particularly for GCpoor regions. The GC content-related CpG deficiency is probably caused by context-dependent deamination of methylated CpG sites. This hypothesis was examined in this study by comparing nucleotide frequencies at CpG flanking positions among invertebrate and vertebrate genomes. The finding is a transition of nucleotide preference of 5＇ T to 5＇ A at the invertebrate-vertebrate boundary, indicating that a large number of CpG sites with 5＇ Ts were depleted because of global DNA methylation developed in vertebrates. At genome level, we investigated CpG observed/expected （obs/exp） values in 500 bp fragments, and found that higher CpG obs/exp value is shown in GC-poor regions of invertebrate genomes （except sea urchin） but in GC-rich sequences of vertebrate genomes. We next compared GC content at CpG flanking positions with genomic average, showing that the GC content is lower than the average in invertebrate genomes, but higher than that in vertebrate genomes. These results indicate that although 5＇ T and 5＇ A are different in inducing deamination of methylated CpG sites, GC content is even more important in affecting the deamination rate. In all the tests, the results of sea urchin are similar to vertebrates perhaps due to its fractional DNA methylation. CpG deficiency is therefore suggested to be mainly a result of high mutation rates of methylated CpG sites in GC-poor regions.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 31070928, 30600198, 30870876 and 81000558)the Guangzhou Scholar Project (Nos. 10A011G and 10A012G)the Scientific Research of Guangzhou Municipal Colleges and Universities (No. 10A211).
文摘Transcription factors（TFs）play critical roles in the development of the nervous system,but the transcriptional regulatory mechanisms of these genes are poorly understood.Here we analyzed 5-kb of the 5＇ flanking genomic DNA sequences of 41 TF genes involved in neuronal development.The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich（GC content60%）promoter with a CpG island.The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence（FGS）;however,more than half（37 of 70）of the GC-rich promoters were located in the proximal region between nucleotides—1 and—500.Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity.This study suggests a potential general mechanism for regulation of TF expression.
文摘Vertebrate genomes are characterized with CpG deficiency, particularly for GCpoor regions. The GC content-related CpG deficiency is probably caused by context-dependent deamination of methylated CpG sites. This hypothesis was examined in this study by comparing nucleotide frequencies at CpG flanking positions among invertebrate and vertebrate genomes. The finding is a transition of nucleotide preference of 5＇ T to 5＇ A at the invertebrate-vertebrate boundary, indicating that a large number of CpG sites with 5＇ Ts were depleted because of global DNA methylation developed in vertebrates. At genome level, we investigated CpG observed/expected （obs/exp） values in 500 bp fragments, and found that higher CpG obs/exp value is shown in GC-poor regions of invertebrate genomes （except sea urchin） but in GC-rich sequences of vertebrate genomes. We next compared GC content at CpG flanking positions with genomic average, showing that the GC content is lower than the average in invertebrate genomes, but higher than that in vertebrate genomes. These results indicate that although 5＇ T and 5＇ A are different in inducing deamination of methylated CpG sites, GC content is even more important in affecting the deamination rate. In all the tests, the results of sea urchin are similar to vertebrates perhaps due to its fractional DNA methylation. CpG deficiency is therefore suggested to be mainly a result of high mutation rates of methylated CpG sites in GC-poor regions.
