研究表明染色质三维结构具有等位效应，即同源染色体之间具有结构差异，但是人们目前并不知道染色质三维结构等位效应是否能够跨代传递。本项目将以模式小鼠的亲代-子代三联体为对象，研究染色质三维结构等位效应从亲代到子代的传递能力（简称为染色质三维结构亲代传递）。首先，本项目将开发新型生物信息学软件，利用遗传变异来分析单倍型染色质互作和识别等位特异性染色质三维结构，为后续研究提供计算工具。其次，本项目将测定三联体小鼠的染色质互作、开放染色质和基因表达数据，研究染色质三维结构亲代传递的总体特征及其对基因表达亲代传递的远程调控作用。最后，本项目将研究转录因子复合体和非编码遗传变异在调控染色质三维结构亲代传递中的作用，并选择部分转录因子结合位点进行实验验证。本项目的顺利开展将揭示染色质三维结构亲代传递的总体特征和分子机理，有助于进一步认识非编码遗传变异引起基因表达亲代传递的远程调控机理。

The researches have shown that the chromatin three-dimensional (3D) structures exhibit allelic effects, i.e., the structural differences between two homologous chromosomes. However, we currently know little on the question whether the allelic effects of chromatin 3D structures can be trans-generationally transmitted. In this project, we will use the parent-offspring trio derived from model mice to study the parents-to-children transmission of allelic effects of chromatin 3D structures, which is called parental transmission of chromatin 3D structures for short. First, by using the genetic variants, we will develop bioinformatics software to process chromatin-interaction haplotype and identify allele-specific chromatin 3D structures, which provides computational tool for following works. Second, we will use Hi-C, ATAC-Seq and RNA-Seq techniques to obtain high-throughput data on chromatin interaction, chromatin accessibility and gene expression. We then investigate the overall characteristics of parental transmission of chromatin 3D structures, and corresponding roles in regulating the parental transmission of gene expression. Last, we will further investigate the regulatory roles of key transcription factors and sequence features of non-coding genetic variants in mediating the parental transmission of chromatin 3D structures, and then experimentally validate the functions by selecting candidate DNA sequences. The works in this project will reveal the overall characteristics and molecular mechanisms for the parental transmission of chromatin 3D structures, helping to better understand the long-range regulatory mechanisms underlying the parental transmission of gene expression caused by non-coding genetic variants.