| Added by | amaraver |
|---|---|
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | The mouse HP1 proteins are essential for preventing liver tumorigenesis |
| Creator | Saksouk et al. |
| Author | Nehmé Saksouk |
| Author | Shefqet Hajdari |
| Author | Yannick Perez |
| Author | Marine Pratlong |
| Author | Célia Barrachina |
| Author | Céline Graber |
| Author | Aliki Zavoriti |
| Author | Amélie Sarrazin |
| Author | Nelly Pirot |
| Author | Jean-Yohan Noël |
| Author | Lakhdar Khellaf |
| Author | Eric Fabbrizio |
| Author | Eric Julien |
| Author | Florence M. Cammas |
| Abstract | Chromatin organization is essential for appropriate interpretation of the genetic information. Here, we demonstrated that the chromatin-associated proteins HP1 are dispensable for hepatocytes survival but are essential within hepatocytes to prevent liver tumor development in mice with HP1? being pivotal in these functions. Yet, we found that the loss of HP1 per se is not sufficient to induce cell transformation but renders cells more resistant to specific stress such as the expression of oncogenes and thus in fine, more prone to cell transformation. Molecular characterization of HP1-Triple KO premalignant livers and BMEL cells revealed that HP1 are essential for the maintenance of heterochromatin organization and for the regulation of specific genes with most of them having well characterized functions in liver functions and homeostasis. We further showed that some specific retrotransposons get reactivated upon loss of HP1, correlating with overexpression of genes in their neighborhood. Interestingly, we found that, although HP1-dependent genes are characterized by enrichment H3K9me3, this mark does not require HP1 for its maintenance and is not sufficient to maintain gene repression in absence of HP1. Finally, we demonstrated that the loss of TRIM28 association with HP1 recapitulated several phenotypes induced by the loss of HP1 including the reactivation of some retrotransposons and the increased incidence of liver cancer development. Altogether, our findings indicate that HP1 proteins act as guardians of liver homeostasis to prevent tumor development by modulating multiple chromatin-associated events within both the heterochromatic and euchromatic compartments, partly through regulation of the corepressor TRIM28 activity. |
| Publication | Oncogene |
| Volume | 39 |
| Issue | 13 |
| Pages | 2676-2691 |
| Date | 2020-03 |
| Journal Abbr | Oncogene |
| Language | eng |
| DOI | 10.1038/s41388-020-1177-8 |
| ISSN | 1476-5594 |
| Library Catalog | PubMed |
| Extra | PMID: 32020053 |
| Tags | Animals, Cell Line, Cell Transformation, Neoplastic, Chromobox Protein Homolog 5, Chromosomal Proteins, Non-Histone, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Hepatocytes, Heterochromatin, Humans, Liver, Liver Neoplasms, Male, Mice, Mice, Knockout, original, Protein Binding, Retroelements, Tripartite Motif-Containing Protein 28 |
| Date Added | 2022/08/31 - 14:33:02 |
| Date Modified | 2022/08/31 - 14:33:11 |
| Notes and Attachments | PubMed entry (Attachment) Submitted Version (Attachment) |
Institut de Recherche en Cancérologie de
