Uncovering the role of histone marks in the aging and senescence of multiple organs at nano scale

At the turn of the century, C.D. Allis moved beyond the double helix and postulated that epigenetic control over phenotypes was animated by a series of alterations to the nucleosome. DNA, tightly wound about histone protein complexes with modifications such as methylated, acetylated, phosphorylated, and ubiquitinated moieties at various residues - referred to as histone marks - became known as the Allis Code, or Histone Code. These histone marks affect higher order structures of DNA, altering transcriptional accessibility, and thus effectively activating or repressing various genes. It has long been observed in histopathology that heterochromatin compactness in the nucleoli may confer stemness and other annotations. However the interplay between histone marks, senotypic markers, and aging. This proposal leverages cutting edge multiplex Structured Illumination Microscopy to probe this question in multiple organ tissues at super-resolution. Results show striking patterns in both overall histone mark intensity between cell types and intranuclear position, offering a new epigenetic dimension to investigate aging, alongside cell morphology and expression of senotypic markers such as P16, P21, and P53. We also demonstrate how these patterns differ between organs and across age groups, marking the first pan-organ multi-omics pathology study using super resolution histone marks. This dataset will serve as a foundational resource for predicting gene accessibility from imaging data alone, affording whole slide data without the need for expensive sequencing methods.

Learning Objectives: 

1. Understand the Allis Histone Code
2. Understand how histone marks correlate with other epigenetic features
3. Predict gene accessibility from imaging data alone