School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
The Leicester International Institute, Dalian University of Technology, Dalian 116000, China.
Nucleic Acids Res. 2024 Jan 5;52(D1):D145-D153. doi: 10.1093/nar/gkad954.
Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.
异染色质在真核生物基因组中发挥着重要作用，例如调节基因、维持基因组完整性和沉默重复 DNA 元件。鉴定全基因组异染色质区域对于研究转录调控至关重要。我们提出了人类异染色质染色质数据库 (HHCDB)，用于根据统一的工作流程存储由特定或组合组蛋白修饰（H3K27me3、H3K9me2、H3K9me3）定义的异染色质区域。从 241 种细胞类型/细胞系和 92 种组织类型的 578 个样本中鉴定出 42399743 个异染色质区域。HHCDB 提供了基因组信息，包括染色质位置、基因结构、转录本、与转录起始位点的距离、相邻基因、CpG 岛、转座元件、3D 基因组结构和功能注释。此外，还分析和整合了来自 73 个单细胞的转录组数据，以探索细胞类型特异性的异染色质相关基因。HHCDB 通过 UCSC 基因组浏览器和我们自主开发的工具提供了丰富的可视化功能。我们还开发了一个专门的在线分析平台，用于挖掘癌症中的差异异染色质区域。我们进行了几项分析来探索癌症特异性异染色质相关基因的功能，包括临床特征分析、免疫细胞浸润分析和药物靶点网络的构建。HHCDB 是研究表观遗传调控、3D 基因组学和发育和疾病中异染色质调控的有价值资源。HHCDB 可在 http://hhcdb.edbc.org/ 免费获取。
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