Living cells maintain stable transcriptional programs while exhibiting plasticity that
allows them to respond to environmental stimuli. The Polycomb repressive complex 2
(PRC2) is a key regulator of chromatin structure that maintains gene silencing through
the methylation of histone H3 on lysine 27 (H3K27me), establishing chromatin-based
memory. Two variants of PRC2 are present in mammalian cells, PRC2-EZH2 which
is predominantly present in differentiating cells, and PRC2-EZH1 that predominates
in post-mitotic tissues.
PRC2-EZH1α/β pathway is involved in the response of muscle cells to oxidative
stress. Atrophied muscle cells respond to oxidative stress by enabling the nuclear
translocation of EED and its assembly with EZH1α and SUZ12. Here we prove that
the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long
noncoding RNA (lncRNA) is required for the assembly of PRC2-EZH1 components.
The absence of MALAT1 significantly decreased the association between EED and
EZH1α proteins. Biochemical analysis shows that the presence of MALAT1 increases
the enzymatic activity of PRC2-EZH1 in vitro.
In addition, we show that the simultaneous expression of PRC2 core components is
necessary for their solubility. The successful expression of PRC2 proteins enables the
execution of several downstream experiments, which will further explain the nature of
the interplay between MALAT1 and PRC2.
|Date of Award||Aug 4 2019|
|Original language||English (US)|
- Biological, Environmental Science and Engineering
|Supervisor||Valerio Orlando (Supervisor)|