Temporal regulation of gene expression through integration of p53 dynamics and modifications

Dan Lu, Marjan Faizi, Bryon Drown, Alina Simerzin, Joshua François, Gary Bradshaw, Neil Kelleher, Ashwini Jambhekar, Jeremy Gunawardena, Galit Lahav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The master regulator of the DNA damage response, the transcription factor p53, orchestrates multiple downstream responses and coordinates repair processes. In response to double-strand DNA breaks, p53 exhibits pulses of expression, but how it achieves temporal coordination of downstream responses remains unclear. Here, we show that p53’s posttranslational modification state is altered between its first and second pulses of expression. We show that acetylations at two sites, K373 and K382, were reduced in the second pulse, and these acetylations differentially affected p53 target genes, resulting in changes in gene expression programs over time. This interplay between dynamics and modification may offer a strategy for cellular hubs like p53 to temporally organize multiple processes in individual cells.

Original languageEnglish (US)
Article numbereadp2229
JournalScience Advances
Volume10
Issue number43
DOIs
StatePublished - Oct 25 2024

ASJC Scopus subject areas

  • General

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