Epigenomics promises to unlock the hidden code of the human genome. As we know, the human genome contains 3 billion letters of G, A, T and Cs, but less than 2% of it has been decoded. To explore the uncharted human genome is like navigating the vast and open ocean, where epigenomics provides the indispensable compass to chart the route.
In the last two decades, members of the UC San Diego Center for Epigenomics have demonstrated that the epigenome, which refers to the collection of all chemical modifications that are deposited to the DNA and chromosomal proteins in each and every cell during the lifespan, provides the crucial information needed to infer the biological activities of the underlying DNA sequences. We have developed high-throughput technologies, by leveraging the rapid advancements of DNA sequencing instruments, to delineate the dynamic epigenome landscape at increasing resolution, scale and efficiency.
Below are a few major milestones along this journey.
2000
- A team led by C4E Director Bing Ren, PhD, reports the first method for genome-wide location analysis of transcription factors, known as ChIP-on-chip, transforming gene regulation studies.
2007
- In a paper published in Nature Genetics, Ren and colleagues identify H3K4me1 as a unique mark of enhancers, enabling their identification in the genome.
- A paper published in Cell maps the binding sites of the insulator protein CTCF in the human genome, revealing its complex function.
2009
- Featured in Nature for their work, Ren and colleagues present the first map of candidate enhancers in the human genome based on histone modification signatures, showing cell-type-dependent histone modifications.
2012
- Another Nature paper identifies topologically associated domains (TADs) as a feature of 3D genome conformation, showing their role in gene regulation.
- Also published in Nature is Ren’s collaborative work to map candidate promoters, enhancers, and CTCF binding sites in the mouse genome, providing a critical resource for gene regulation studies.
2013
- Nature publishes Ren’s collaborative work to map more than one million chromatin contacts in the human genome, showing the stability of chromatin architecture within a cell lineage.
2015
- Another Nature paper explains Ren and colleagues' work to analyze dynamic chromatin architecture during stem cell differentiation, correlating chromatin contacts with gene expression changes.
2017
- UC San Diego Health Sciences invests $8M to establish a research center focused on the development and application of epigenomic technologies directed by Bing Ren, PhD.
- The Center’s Scientific Advisory Board is established to guide Center research and implementation.
- Installed an automated liquid handling system, the Center’s first instrumentation workhorse.
- The first ensemble ATAC-seq assay and single cell ATAC-seq assay, flagship offerings for the Center, completed and analyzed.
- Data generation begins for NIH BRAIN Initiative’s BICCN (BRAIN Initiative Cell Census Network) study to help identify classes of cells in mouse brain and understand their function.
- The Center’s services unit was established to bring Epigenomic and Single-cell Genomic Services to the UC San Diego community and beyond.
2018
- Generated 1000 ensemble ATAC-seq libraries, achieving data production milestone.
- Selected as data generation center for LungMAP 2 to create molecular maps to enable improved understanding of defined cell types in human lungs.
- Joined HIRN as a data generation center to investigate phenomena related to the loss of functional beta cell mass in Type 1 Diabetes (T1D).
- Center officially launches fee-for-service offerings for bulk ATAC-seq, single-cell ATAC-seq, and single-cell RNA-seq.
2019
- Center staff visits the laboratory of Xiaowei Zhuang to learn advanced spatial genomics methods such as MERFISH
- Installed two spatial genomics imaging systems at the Center
- First DNA-MERFISH and RNA-MERFISH datasets are generated
- Data generation begins for NIH BRAIN Initiative’s BICCN to contribute to cell census data collection and development of relevant tools for cell types for the human brain
2020
- sciATAC-seq data generation complete for the >25 human tissues from 4 donors resulting in the largest human cell-type resolved ATAC-seq dataset to date.
- The web portal cATLAS (Cis-relugatory atlas) is launched to rapidly share single-cell data from the Center with the larger research community.
- The web portal lungepigenome.org is launched to share lung single-cell data and to empower the lung research community.
- Generated >1000 single-cell ATAC-seq libraries, meeting data production milestone.
- The Center hosts the first pandemic-era San Diego Chromatin club virtual seminar featuring director Dr. Bing Ren with > 500 attendee’s followed by thousands of views on YouYube.
- eLife publication – the first from LungMap 2 collaborative work: “Single cell multiomic profiling of human lung reveals cell type-specific and age-dynamic control of SARS-CoV2 host genes.”
- Generated the first RNA-MERFISH dataset using primary.
- Also featured in Nature is work by Ren and colleagues to determine dynamic chromatin landscapes in 12 mouse fetal tissues, providing a resource for developmental gene regulation studies.
2021
- Spatial Genomics services unit is established for external collaboration and to provide spatial genomics services the UC San Diego and beyond.
- Nature Genetics publication – the first from HIRN collaborative work: “Single-cell chromatin accessibility identifies pancreatic islet cell type– and state-specific regulatory programs of diabetes risk.”
- Science Advances publication – the first from collaborative work focused on the human heart: “Cardiac cell type–specific gene regulatory programs and disease risk association.”
- Nature Genetics publication – the first paper featuring contributions from the spatial genomics platform: “CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains.”
- Nature publication – a landmark publication from the Center’s efforts as part of the NIH BRAIN Initiative’s BICCN: “An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum.”
- Ren and colleagues conduct a systematic analysis of transcription factor binding to noncoding variants in the human genome, improving predictive models.
- Cell publishes work by Ren and colleagues to create a single-cell atlas of chromatin accessibility in the human genome, aiding functional interpretation of GWAS results.
2023
- Science publishes Ren’s collaborative work to explore chromatin landscapes in the human brain, linking cell types to neuropsychiatric disorders and developing predictive models.