NOMe-HiC：在同一 DNA 分子中联合分析遗传变异、DNA 甲基化、染色质可及性和 3D 基因组。

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Genome Biol. 2023 Mar 16;24(1):50. doi: 10.1186/s13059-023-02889-x.

Cis-regulatory elements are coordinated to regulate the expression of their targeted genes. However, the joint measurement of cis-regulatory elements' activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single-nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.

顺式调控元件协同调控其靶基因的表达。然而，当前的测序方法限制了顺式调控元件活性及其在空间上相互作用的联合测量。我们描述了一种方法，NOMe-HiC，它可以在单个测定中同时捕获来自同一 DNA 分子的单核苷酸多态性、DNA 甲基化、染色质可及性（GpC 甲基转移酶足迹）和染色体构象变化，以及转录组。NOMe-HiC 与不同分子测量的最先进的单组学检测方法高度一致，并揭示了空间上接近的远端基因组片段的协调染色质可及性和新型长距离等位基因特异性染色质可及性。