ICTS:29641

Video URL

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactio…

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth

(2024). Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth. SciVideos. https://youtu.be/R9UnAISaHsA

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth. SciVideos, Sep. 18, 2024, https://youtu.be/R9UnAISaHsA 

          @misc{ scivideos_ICTS:29641,
            doi = {},
            url = {https://youtu.be/R9UnAISaHsA},
            author = {},
            keywords = {},
            language = {en},
            title = {Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth},
            publisher = {},
            year = {2024},
            month = {sep},
            note = {ICTS:29641 see, \url{https://scivideos.org/icts-tifr/29641}}
          }
Seng Chuan Tang
Talk numberICTS:29641
Source RepositoryICTS-TIFR
Source EventInterdisciplinary aspects of chromatin organization and gene regulation
Collection

Abstract

Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers needs to be elucidated, such as whether they can form “super-silencers” and whether they are linked to cancer progression. Here, through interrogating two putative silencer components of FGF18 gene, we found that two nearby silencers can cooperate via compensatory chromatin interactions to form a “super-silencer”. Furthermore, double knockout of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To perturb the “super-silencers”, we applied combinational treatment of an EZH2 inhibitor GSK343, and a REST inhibitor, X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while the use of one inhibitor by itself only showed mild changes. Such changes in TADs and loops were associated with reduced CTCF and TOP2A mRNA levels. Moreover, GSK343 and X5050 synergistically upregulated...