神经管畸形鼠H3K27me3与叶酸代谢相关基因甲基化作用研究

Neural tube defeets(NTDs) is a group common and extremely serious birth defects, is also one of the reason that caused fetus and infans death or severe disability. Ningxia province is a region with high incidence. Folic acid is the most important enviroment factor to rescue NTDs. Some research confirmed that H3K27me3 was the epigenetic marks that was the switch from proliferation to differeniationthe of neuron; Folic acid played the role through H3K27 methylation.The pathogenesis of NTDs and the protect role of folic acid are not clearly.The relationship between Histone modifiy and DNA methylation is a exciting thought. Our research team had bulit the animal model of NTDs, and became initial conscious of ultrastructure and DNA methylation of rats NTDs fetus. This task in our research is about the relationship between Histone modify and DNA methylation of rats NTDs. We will explore the mutual relation between H3K27me3 and folate metabolism pathway genes,using the CHiP-seq, iRNA, plasmid transfection,MeDIp technique etc, from understanding the pathogenesis of cell level to seeking the epigenetic mark of tissue level. So we can ascertain the role of H3K27me3 and folate metabolism pathway genes,and search the new clue of the pathgenesis and new pathway for seeking the new biomarker with NTDs.

神经管畸形(neural tube defect，NTDs)是造成胎儿和婴儿死亡以及儿童残疾的常见出生缺陷，宁夏是NTDs高发区。叶酸是避免NTDs发生最重要的环境因素，但神经管畸形的发病机制及叶酸对NTDs保护机制尚不清楚，有研究证实H3K27me3是神经元分化中起"开关"作用的表观遗传学标志物，叶酸通过改变H3K27甲基化而参与这一过程。本课题组已成功制作了神经管畸形大鼠模型，在神经管超微结构观察及DNA甲基化方面取得初步结果。本课题拟围绕探讨叶酸干预下H3K27me3与叶酸代谢相关基因甲基化相互作用的研究目标，采用CHiP-seq、iRNA、质粒转染、MeDIp等技术，从细胞水平的机制研究过渡到组织层面表观遗传学标志物的筛寻，以确定H3K27me3和叶酸代谢相关基因DNA甲基化在神经管畸形发生中的作用和地位，为研究神经管畸形发生机制并进一步寻找其分子标志物提供实验依据和新思路。

神经管畸形(neural tube defect，NTDs)是造成胎儿和婴儿死亡以及儿童残疾的常见出生缺陷，宁夏是NTDs高发区。叶酸是避免NTDs发生最重要的环境因素，但神经管畸形的发病机制及叶酸对NTDs保护机制尚不清楚，有研究证实H3K27me3是神经元分化中起“开关”作用的表观遗传学标志物，叶酸通过改变H3K27甲基化而参与这一过程。本课题组成功制作了神经管畸形大鼠模型，在神经管超微结构观察及DNA甲基化方面取得初步结果。本课题拟围绕探讨叶酸干预下H3K27me3与叶酸代谢相关基因甲基化相互作用的研究目标，采用CHiP-seq、iRNA、质粒转染、western blot、qRT-PCR等技术，从细胞水平的机制研究过渡到组织层面表观遗传学标志物的筛寻，以确定H3K27me3和叶酸代谢相关基因DNA甲基化在神经管畸形发生中的作用和地位，为研究神经管畸形发生机制并进一步寻找其分子标志物提供实验依据和新思路。