Genomic retargeting of p53 and CTCF is associated with transcriptional changes during oncogenic HRas-induced transformation

Michal Schwartz, Avital Sarusi Portugez, Bracha Zukerman Attia, Miriam Tannenbaum, Leslie Cohen, Olga Loza, Emily Chase, Yousef Turman, Tommy Kaplan, Zaidoun Salah, Ofir Hakim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Gene transcription is regulated by distant regulatory elements via combinatorial binding of transcription factors. It is increasingly recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene-induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional changes associated with this process. Using Hi-C data, we observe spatial coupling between differentially expressed genes and their differentially accessible regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as determinants of transcriptional alterations at the early stages of oncogenic HRas-induced transformation in human mammary epithelial cells. Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.

Original languageAmerican English
Article number696
JournalCommunications Biology
Volume3
Issue number1
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

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