We create and instantiate technologies to enable both large-scale mapping and mechanistic understanding of the epigenome. These fit into the broader toolkit of the Cell Circuits & Epigenomics programs. We have instantiated some of our core technologies for large scale epigenome mapping projects, such as ENCODE4. We also devote significant effort to protocol development in order to work with diverse, complex and rare tissues and cell types.
We currently work with many collaborators to create epigenetic profiles of both healthy and diseased cell populations using the following technologies.
Transcriptomics
- RNA-Seq
- Single-cell RNA-Seq (including CEL-Seq2 and Seq-well from the Shalek lab at MIT)
Chromatin mapping
- ChIP-Seq (transcription factors, chromatin regulators, and histone modifications)
- MINT-ChIP
- Single-molecule decoding of modified nucleosomes
- ATAC-Seq
- Microfluidic-ChIP
DNA methylation mapping
- Reduced representation bisulfite sequencing (RRBS; including single-cell RRBS)
- Whole-genome bisulfite sequencing (WGBS)
- Targeted bisulfite sequencing
- ChIP-bisulfite sequencing
Genome topology
Other Assays
- Dual (RRBS+RNA)-Seq of low-input samples
- Massively parallel reporter assay (MPRA) of enhancer activity
Perturbations
- Epigenome engineering
- Chromatin regulator CRISPR screens
- High throughput small molecule targeting of chromatin factors
How to work with us
The Epigenomics Program operates on a collaborative model. To work with us, please contact Liz Gaskell, Chuck Epstein, or Andi Gnirke with a brief description of your project, your scientific question, funding opportunities, and an idea of scale.
See Broad Technology Labs for specialized service facility epigenomics products.
Key papers
Shema E, et al. Single-molecule decoding of combinatorially modified nucleosomes. Science. 2016.
van Galen P, et al. A multiplexed system for quantitative comparisons of chromatin landscapes. Mol Cell. 2016.
Rotem A, Ram O, Shoresh N, et al. Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state. Nat Biotechnol. 2015.
Mendenhall EM, et al. Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol. 2013.
Ziller MJ, et al. Targeted bisulfite sequencing of the dynamic DNA methylome. Epigenetics Chromatin. 2016.
Ziller MJ, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013.
Brinkman AB, et al. Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Res. 2012.
Boyle P, Clement K, Gu H, et al. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling. Genome Biol. 2012.
Meissner A, Mikkelsen TS, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008.
