Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues
While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases.
Authors
- Axel Visel (ORCID: https://orcid.org/0000-0002-4130-7784)
- Ming Hu (ORCID: https://orcid.org/0000-0003-0987-2916)
- Shreya Mishra (ORCID: https://orcid.org/0000-0003-3964-7082)
- Ramya Raviram (ORCID: https://orcid.org/0000-0002-5450-1455)
- Diane E. Dickel (ORCID: https://orcid.org/0000-0001-5497-6824)
- Yunjiang Qiu (ORCID: https://orcid.org/0000-0002-0539-9714)
- Nathan R. Zemke (ORCID: https://orcid.org/0000-0002-6326-5925)
- David U. Gorkin (ORCID: https://orcid.org/0000-0003-4944-4107)
- L Pennacchio (ORCID: https://orcid.org/0000-0002-8748-3732)
- Anthony D. Schmitt (ORCID: https://orcid.org/0000-0002-3818-1156)
- Armen Abnousi (ORCID: https://orcid.org/0000-0003-1822-0928)
- Yang Eric Li (ORCID: https://orcid.org/0000-0001-6997-6018)
- Ivan Jurić (ORCID: https://orcid.org/0000-0002-1076-6320)
- Bing Ren (ORCID: https://orcid.org/0000-0002-5435-1127)
- Yanxiao Zhang (ORCID: https://orcid.org/0000-0001-9618-637X)
- Rong Hu (ORCID: https://orcid.org/0000-0002-0660-0387)
- Ziyin Chen (ORCID: https://orcid.org/0000-0002-5760-4177)
- Rongxin Fang (ORCID: https://orcid.org/0000-0003-0107-7504)
- Lindsay Lee (ORCID: https://orcid.org/0000-0001-5591-6233)
- Yuan Zhao
- Miao Yu (ORCID: https://orcid.org/0009-0003-2147-3413)
Institutions
- Cleveland Clinic (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Lawrence Berkeley National Laboratory (US)
- Emory University (US)
- University of California, Merced (US)
- Bellevue College (US)
- Ludwig Cancer Research (BE)
- Joint Genome Institute (US)
- Washington University in St. Louis (US)
- Fudan University (CN)
- Westlake University (CN)
- University of California San Diego (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Sana Biotechnology (United States) (US)
- Arima Genomics (United States) (US)
- Ludwig Cancer Research (US)
- New York Genome Center (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Nature Structural & Molecular Biology
- Published
- 2024-12-16
- DOI
- https://doi.org/10.1038/s41594-024-01431-2
- Citations
- 6
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- U.S. Department of Energy
- National Institutes of Health
- Lawrence Berkeley National Laboratory