美国哈德逊-阿尔法生物技术研究所Richard M. Myers和Gregory M. Cooper小组合作的研究，完成了对人脑中转录因子（TF）结合与功能的多组学分析。这一研究成果发表在2024年6月3日出版的国际学术期刊《自然-神经科学》上。

研究人员利用几个死者的大块脑组织和不同区域的细胞核生产了一个多组学资源（ChIP-seq、ATAC-seq、RNA-seq、DNA甲基化）库，其中包括100多个TF结合图。研究证明，在识别和移除高TF占有区域后，TF活性的测量结果（包括主题识别和基因表达建模）得到了改善。

此外，预测性TF结合模型也证明了这些高占据位点的偏好性。神经元TF SATB2和TBR1结合了占据了这些位点的独特区域，并促进了神经元基因的表达。包含TBR1和PKNOX1在内的TF结合位点富含与神经精神疾病相关的风险变异，这些风险变异主要存在于神经元中。这项名为"脑TF"的研究为今后研究特定TF，在调节人脑基因表达中的功能提供了强大的资源。

据悉，TF是调控大脑功能至关重要的基因表达程序，但目前缺乏有关人类脑组织中TF结合的详细信息。

附：英文原文

Title: Multiomic profiling of transcription factor binding and function in human brain

Author: Loupe, Jacob M., Anderson, Ashlyn G., Rizzardi, Lindsay F., Rodriguez-Nunez, Ivan, Moyers, Belle, Trausch-Lowther, Katie, Jain, Rashmi, Bunney, William E., Bunney, Blynn G., Cartagena, Preston, Sequeira, Adolfo, Watson, Stanley J., Akil, Huda, Cooper, Gregory M., Myers, Richard M.

Issue&Volume: 2024-06-03

Abstract: Transcription factors (TFs) orchestrate gene expression programs crucial for brain function, but we lack detailed information about TF binding in human brain tissue. We generated a multiomic resource (ChIP–seq, ATAC-seq, RNA-seq, DNA methylation) on bulk tissues and sorted nuclei from several postmortem brain regions, including binding maps for more than 100 TFs. We demonstrate improved measurements of TF activity, including motif recognition and gene expression modeling, upon identification and removal of high TF occupancy regions. Further, predictive TF binding models demonstrate a bias for these high-occupancy sites. Neuronal TFs SATB2 and TBR1 bind unique regions depleted for such sites and promote neuronal gene expression. Binding sites for TFs, including TBR1 and PKNOX1, are enriched for risk variants associated with neuropsychiatric disorders, predominantly in neurons. This work, titled BrainTF, is a powerful resource for future studies seeking to understand the roles of specific TFs in regulating gene expression in the human brain.

DOI: 10.1038/s41593-024-01658-8

Source: https://www.nature.com/articles/s41593-024-01658-8