First name
Chiara
Last name
Locarno
Year of Study
Research Center
Thesis Title
Proteomic identification of the transcription factors Ikaros and Aiolos as new Myc interactors on chromatin
Thesis Abstract
Myc is a transcription factor that plays a key role in many cellular functions. When
deregulated, it becomes a potent oncogene and a hallmark of many human cancers.
Although its activity has been proven to strongly depend on many cofactors, we are still far
from a comprehensive understanding of Myc’s mechanisms of action in transcriptional
control. Moreover, since Myc itself is not easily druggable, targeting its cofactors or
downstream effectors may constitute a more promising therapeutic strategy in Myc-driven
tumors. Here, we have used the Chromatin Proteomics (ChroP) technology to identify new
Myc interactors. Among the list of identified candidates, we have chosen to focus our
attention on two lymphocyte specific transcription factors, Ikaros and Aiolos. We validated
the interaction of Myc with these factors and started to study its functional meaning. Our
working hypothesis is that Myc and Ikaros/Aiolos antagonize each other on chromatin at
selected target loci. We were able to identify a subset of genes regulated in opposite
manners by Ikaros and Myc, involved mainly in cell cycle regulation, metabolism of lipids
and metabolic stress response; the next step will be to study more in depth the mechanisms
behind their regulation and their functional significance.
deregulated, it becomes a potent oncogene and a hallmark of many human cancers.
Although its activity has been proven to strongly depend on many cofactors, we are still far
from a comprehensive understanding of Myc’s mechanisms of action in transcriptional
control. Moreover, since Myc itself is not easily druggable, targeting its cofactors or
downstream effectors may constitute a more promising therapeutic strategy in Myc-driven
tumors. Here, we have used the Chromatin Proteomics (ChroP) technology to identify new
Myc interactors. Among the list of identified candidates, we have chosen to focus our
attention on two lymphocyte specific transcription factors, Ikaros and Aiolos. We validated
the interaction of Myc with these factors and started to study its functional meaning. Our
working hypothesis is that Myc and Ikaros/Aiolos antagonize each other on chromatin at
selected target loci. We were able to identify a subset of genes regulated in opposite
manners by Ikaros and Myc, involved mainly in cell cycle regulation, metabolism of lipids
and metabolic stress response; the next step will be to study more in depth the mechanisms
behind their regulation and their functional significance.
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