PT  - JOURNAL ARTICLE
AU  - Roberto Ferrarese
AU  - Annalisa Izzo
AU  - Geoffroy Andrieux
AU  - Simon Lagies
AU  - Johanna Paulina Bartmuss
AU  - Anie Priscilla Masilamani
AU  - Alix Wasilenko
AU  - Daniela Osti
AU  - Stefania Faletti
AU  - Rana Schulzki
AU  - Shuai Yuan
AU  - Eva Kling
AU  - Valentino Ribecco
AU  - Dieter Henrik Heiland
AU  - Stefan Tholen
AU  - Marco Prinz
AU  - Giuliana Pelicci
AU  - Bernd Kammerer
AU  - Melanie Boerries
AU  - Maria Stella Carro
TI  - ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma
AID  - 10.26508/lsa.202201400
DP  - 2023 Jan 01
TA  - Life Science Alliance
PG  - e202201400
VI  - 6
IP  - 1
4099  - https://www.life-science-alliance.org/content/6/1/e202201400.short
4100  - https://www.life-science-alliance.org/content/6/1/e202201400.full
SO  - Life Sci. Alliance2023 Jan 01; 6
AB  - Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression of enzymes involved in fatty acid and cholesterol synthesis. Yet, little is known about the precise mechanism regulating SREBP gene expression in glioblastoma. Here, we show that a novel interaction between the co-activator/co-repressor CTBP and the tumor suppressor ZBTB18 regulates the expression of SREBP genes. In line with our findings, metabolic assays and glucose tracing analysis confirm the reduction in several phospholipid species upon ZBTB18 expression. Our study identifies CTBP1/2 and LSD1 as co-activators of SREBP genes and indicates that the functional activity of the CTBP-LSD1 complex is altered by ZBTB18. ZBTB18 binding to the SREBP gene promoters is associated with reduced LSD1 demethylase activity of H3K4me2 and H3K9me2 marks. Concomitantly, the interaction between LSD1, CTBP, and ZNF217 is increased, suggesting that ZBTB18 promotes LSD1 scaffolding function. Our results outline a new epigenetic mechanism enrolled by ZBTB18 and its co-factors to regulate fatty acid synthesis that could be targeted to treat glioblastoma patients.