Nucleosome-scale p53-hormone receptor grammar distributed by Alu elements

The tumor suppressor protein p53, along with estrogen receptor and androgen receptor transcription factors, controls growth in a sex-specific, hormone-responsive way within various tissues such as breast, prostate, and muscle tissue. Researchers used a transcriptional regulation model to study the co-regulation between p53 and hormone receptors across different cell types, identifying an enrichment specifically in mammary and muscle cells.

Evidence from the sequence, structure, and epigenomics of these regulatory regions suggests a functional 73-base pair p53-estrogen receptor grammar, extending from nucleosome entry/exit to a specific region known as the dyad. In contrast, the p53-androgen receptor grammar spans 146 base pairs. When examining a functional breast cancer enhancer regulating the Cyclin D gene, the findings indicate that varying spacing between these elements results in reduced predicted p53 binding.

A genome-wide analysis further revealed that Alu sequences play a major role in disseminating these regulatory grammars, particularly in genes associated with the mTORC1 pathway. The study also highlights an evolutionary link between primate body-size sexual dimorphism and muscle aging.