• The functional outputs of the genome depend on its epigenetic profile, which both affects and is affected by the 3D genome organization.
• No previous technology allows locus-specific epigenetic profiling in single cells while retaining the 3D genome organization.
• Dr. Siyuan (Steven) Wang’s lab at Yale invented an image-based in-situ epigenetic detection method that detects locus-specific epigenetic marks in single cells at a given genomic locus.
• His lab further expanded the method to an epigenetic profiling technique termed Epi-mFISH that enables combined profiling of epigenetic mark at numerous genomic loci and mapping of 3D chromatin organization in single cells.
• Epi-mFISH expands our existing image-based spatial genomics and transcriptomics tool kit to single-cell spatial epigenomic profiling.
• Intellectual Property: Patent application pending
• Reference: Manuscript in preparation

Figures

A) Application of Epi-mFISH to a genomic locus on human ChrX in RPE1 cell line with antibodies targeting either H3K27me3 (top) or H3K9me3 (bottom). The copy of the locus on inactive ChrX (Xi) is known to have H3K27me3 but not H3K9me3, which is faithfully captured by Epi-mFISH, but not by common co-immunofluorescence (IF).

B) The epigenetic states of 22 genomic loci detected by EpimFISH highly correlate with ChIP-seq data at the population averaged level in IMR90 cell line. Also note H3K27Ac was targeted in one of the two tests. So Epi-mFISH is compatible with both active (e.g. H3K27Ac) and inactive (e.g. H3K9me3, H3K27me3) epigenetic marks