Archival chromatin sequencing in formalin-fixed mouse specimens

Formalin induces inter- and intra-molecular crosslinks within exposed cells. This cross-linking can be exploited to characterise chromatin state as in the FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) and MNase (micrococcal nuclease) assays. Here, we optimised the FAIRE and MNase assays for application upon heavily-fixed tissues as is typically found in historical formalin-preserved museum specimens. We demonstrate these assays in formalin-fixed mouse specimens and compare the chromatin signatures to specimen-matched fresh tissues. We found that heavy formalin fixation modulates rather than eliminates signatures of differential chromatin accessibility and that these chromatin profiles are reproducible, tissue-specific and sex-specific in vertebrate specimens. Overall design: RNA-Seq of Mus musculus liver tissue in two genetic backgrounds (C57BL/6 and wild caught).