UT Southwestern Center for Regulatory Element Variation and Function
Overview
The UTSW Center for Regulatory Element Variation and Function is part of the Impact of Genomic Variation on Function (IGVF) Consortium (an NHGRI multimillion-dollar, multi-center collaborative initiative for 2021 through 2026). The primary goal of this Center is to systematically catalog molecular and cellular phenotypes for disease-associated enhancers in human development, with a focus on gaining insights into mechanisms of non-classical human genetics and gene regulation.
Objectives
To build a generalizable framework to understanding the impact of human genetic variation on function, we propose a high throughput perturbation platform with three primary goals: (1) Contribute to a variant/element/phenotype catalog with relevance to diseases of human development, focusing on elements genetically associated with congenital heart disease (cardiomyocytes), autism (neurons), and placental defects (trophoblasts); (2) Contribute to a variant/element/phenotype catalog for non-canonical human genetics, focusing on two understudied topics in human genetics: pleiotropic effects and non-cell autonomous effects; and (3) Contribute to a variant/element/phenotype catalog with relevance to mechanisms of gene regulation, focusing on enhancer RNAs.
News Coverage
Sept. 9, 2021
NIH providing $185 million for research to advance understanding of how human genome functions
Oct. 25, 2021
UT Southwestern Team Awarded $8.8M to Participate in Genomic Variation Consortium
Mar. 8, 2022
Single protein prompts mature brain cells to regenerate multiple cell types
Sept. 19, 2022
UTSW researchers use DNA analysis to diagnose subtypes of heart disease
Apr. 14, 2023
UTSW scientists helped map the human genome 20 years ago. It changed medicine forever (Subscription required)
UT Southwestern Personnel
Developmental Biology
Cardiac dev, gene regulation
Neural dev/disorders
Early embryonic development
High Throughput Perturbation
Enhancers, single-cell
High throughput screening
Data coordination
Gene Regulation
Enhancers, placenta
Publications
Li, Boxun; Hon, Gary C. Single-Cell Genomics: Catalyst for Cell Fate Engineering. Frontiers in Bioengineering and Biotechnology 2021 Oct 18; 9:748942.
Wang, Yihan; Xie, Shiqi; Armendariz, Daniel; Hon, Gary C. Computational identification of clonal cells in single-cell CRISPR screens. BMC Genomics 2022 Feb 15; 23(1):135.
Zhang, Yunjia; Li, Boxun; Cananzi, Sergio; Han, Chuanhui; Wang, Lei-Lei; Zou, Yuhua; Fu, Yang-Xin; Hon, Gary C; Zhang, Chun-Li. A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum. Proceedings of the National Academy of Sciences of the United States of America 2022 Mar 15; 119(11): e2107339119.
Hanchard, Neil A; Chahrour, Maria; de Vries, Jantina. Tailored community engagement to address the genetics diversity gap. Med (New York, N.Y.) 2022 Jun 10; 3(6):369-370.
Hou, Tim Y; Kraus, W Lee. Analysis of estrogen-regulated enhancer RNAs identifies a functional motif required for enhancer assembly and gene expression. Cell Reports 2022 Jun 14; 39(11):110944.
Bhattacharyya, Samadrita; Duan, Jialei; Vela, Ryan J; Bhakta, Minoti; Bajona, Pietro; Mammen, Pradeep P A; Hon, Gary C; Munshi, Nikhil V. Accurate classification of cardiomyopathy diagnosis by chromatin accessibility. Circulation 2022 Sep 13; 146(11): 878-881.
Hsieh, Hsi-Hsien; Yao, Huiyu; Ma, Yue; Zhang, Yuannyu; Xiao, Xue; Stephens, Helen; Wajahat, Naureen; Chung, Stephen S; Xu, Lin; Xu, Jian; Rampal, Raajit K; Huang, Lily Jun-Shen. Epo-IGF1R cross talk expands stress-specific progenitors in regenerative erythropoiesis and myeloproliferative neoplasm. Blood 2022 Dec 1; 140(22):2371-2384.
Cooley, Anne; Madhukaran, ShanmugaPriyaa; Stroebele, Elizabeth; Colon Caraballo, Mariano; Wang, Lei; Akgul, Yucel; Hon, Gary C; Mahendroo, Mala. Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption. iScience 2023 Jan 12; 26(2):105953.
Wang, Lin; Dela Rosa, Jared Gabriel L; Munshi, Nikhil V. Protocol for inducing cellular ablation in the mouse atrioventricular conduction system. STAR Protocols 2023 Mar 11; 4(1):102145.
Armendariz, Daniel A; Goetsch, Sean C; Sundarrajan, Anjana; Sivakumar, Sushama; Wang, Yihan; Xie, Shiqi; Munshi, Nikhil V; Hon, Gary C. CHD-associated enhancers shape human cardiomyocyte lineage commitment. eLife 2023 Apr 25; 12:e86206.
IGVF Consortium. (Writing group included Gary C. Hon, Nikhil Munshi, and Maria Chahrour.) The Impact of Genomic Variation on Function (IGVF) Consortium. ArXiv 2023 Jul 24; arXiv:2307.13708v1.
Armendariz, Daniel A; Sundarrajan, Anjana; Hon, Gary C. Breaking enhancers to gain insights into developmental defects. eLife 2023 Jul 27; 12:e88187.
Owen, David M; Kwon, Minjung; Huang, Xuan; Nagari, Anusha; Nandu, Tulip; Kraus, W Lee. Genome-wide identification of transcriptional enhancers during human placental development and association with function, differentiation, and disease. Biology of Reproduction 2023 Sep 23; 109(6):965–981.
Peng, Jun; Yu, Liming; Huang, Linzhang; Paschoal, Vivian A; Chu, Haiyan; de Souza, Camila O; Varre, Joseph V; Oh, Da Young; Kohler, Jennifer J; Xiao, Xue; Xu, Lin; Holland, William L; Shaul, Philip W; Mineo, Chieko. Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle. Molecular Metabolism 2023 Sep 28; 78:101812.
Lafita-Navarro, M Carmen; Hao, Yi-Heng; Jiang, Chunhui; Jang, Seoyeon; Chang, Tsung-Cheng; Brown, Isabella N; Venkateswaran, Niranjan; Maurais, Elizabeth; Stachera, Weronika; Zhang, Yanfeng; Mundy, Dorothy; Han, Jungsoo; Tran, Vanna M; Mettlen, Marcel; Xu, Lin; Woodruff, Jeffrey B; Grishin, Nick V; Kinch, Lisa; Mendell, Joshua T; Buszczak, Michael; Conacci-Sorrell, Maralice. ZNF692 organizes a hub specialized in 40S ribosomal subunit maturation enhancing translation in rapidly proliferating cells. Cell Reports 2023 Oct 31; 42(10):113280.
Wang, Yihan; Armendariz, Daniel; Wang, Lei; Zhao, Huan; Xie, Shiqi; Hon, Gary C. Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes. bioRxiv 2023 Nov 20:2023.11.20.567880.
Jiang, Xi; Dong, Lei; Wang, Shidan; Wen, Zhuoyu; Chen, Mingyi; Xu, Lin; Xiao, Guanghua; Li, Qiwei. Reconstructing Spatial Transcriptomics at the Single-cell Resolution with BayesDeep. bioRxiv 2023 Dec 8:2023.12.07.570715.
Wei, Yulei; Zhang, E; Yu, Leqian; Ci, Baiquan; Sakurai, Masahiro; Guo, Lei; Zhang, Xin; Lin, Sirui; Takii, Shino; Liu, Lizhong; Liu, Jian; Schmitz, Daniel A; Su, Ting; Zhang, Junmei; Shen, Qiaoyan; Ding, Yi; Zhan, Linfeng; Sun, Hai-Xi; Zhang, Canbin; Xu, Lin; Okamura, Daiji; Ji, Weizhi; Tan, Tao; Wu, Jun. Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture. Cell 2023 Dec 21; 186(26):5859-5875.
Du, Peng; Wu, Jun. Hallmarks of totipotent and pluripotent stem cell states. Cell Stem Cell 2024 Mar 7; 31(3):312-333.
Jiang, Xi; Wang, Shidan; Guo, Lei; Zhu, Bencong; Wen, Zhuoyu; Jia, Liwei; Xu, Lin; Xiao, Guanghua; Li, Qiwei. iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis. Genome Biology 2024 Jun 6; 25:147.
Guo, Yanghong; Yu, Lei; Guo, Lei; Xu, Lin; Li, Qiwei. A Regularized Bayesian Dirichlet-multinomial Regression Model for Integrating Single-cell-level Omics and Patient-level Clinical Study Data. bioRxiv 2024 Jun 6:2024.06.04.597391.
Wu, Jun; Fu, Jianping. Toward developing human organs via embryo models and chimeras. Cell 2024 Jun 20; 187(13):3194-3219.
Lu, Zeyu; Xu, Lin; Wang, Xinlei. BIT: Bayesian Identification of Transcriptional Regulators from Epigenomics-Based Query Region Sets. bioRxiv 2024 Oct 8:2024.06.02.597061.