Nucleosome-scale p53-hormone receptor grammar distributed by Alu elements
- 1Columbia University
Abstract
The tumor suppressor p53 and the transcription factors estrogen receptor and androgen receptor regulate growth in a sex-dependent hormone-responsive manner, as in breast and prostate tumors and muscle tissue. Using a model of transcriptional regulation, we investigated co-regulation between p53 and hormone receptors in different cellular contexts and highlight an enrichment in mammary and muscle cell types. Sequence, structural and epigenomic evidence demonstrate a broadly distributed functional 73-bp p53-estrogen receptor grammar spanning nucleosome entry/exit to dyad, while p53-androgen receptor grammar spans 146 bp. At a functional breast cancer enhancer regulating Cyclin D, varied spacing led to lower predicted p53 binding. Genome-wide analysis found a major role of Alu sequences in distributing this grammar, in particular in mTORC1 pathway genes, with an evolutionary association of primate body-size sexual dimorphism and muscle aging.
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BibTeX
@misc{fu2026nucleosomescale,
title = {{Nucleosome-scale p53-hormone receptor grammar distributed by Alu elements}},
author = {X. Fu and Q. Cai and P. Satya and R. Rabadan and A. J. Levine},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754600},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754600v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Nucleosome-scale p53-hormone receptor grammar distributed by Alu elements
AU - X. Fu
AU - Q. Cai
AU - P. Satya
AU - R. Rabadan
AU - A. J. Levine
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754600
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754600v1
AB - The tumor suppressor p53 and the transcription factors estrogen receptor and androgen receptor regulate growth in a sex-dependent hormone-responsive manner, as in breast and prostate tumors and muscle tissue. Using a model of transcriptional regulation, we investigated co-regulation between p53 and hormone receptors in different cellular contexts and highlight an enrichment in mammary and muscle cell types. Sequence, structural and epigenomic evidence demonstrate a broadly distributed functional 73-bp p53-estrogen receptor grammar spanning nucleosome entry/exit to dyad, while p53-androgen receptor grammar spans 146 bp. At a functional breast cancer enhancer regulating Cyclin D, varied spacing led to lower predicted p53 binding. Genome-wide analysis found a major role of Alu sequences in distributing this grammar, in particular in mTORC1 pathway genes, with an evolutionary association of primate body-size sexual dimorphism and muscle aging.
ER -