Histone demethylases in development and in cancer
Luisa DI STEFANO
CR1 05 61 55 85 99
- Carole IAMPIETRO
- Denis JULLIEN
- Julie LEPESANT
In recent years, the histone lysine demethylase LSD1 has emerged as a key chromatin regulator. LSD1 plays an essential role in regulating cell fate and differentiation and it is often deregulated in cancer. However, our understanding of the biological role of LSD1 is still incomplete. Our goal is to shed light on the mechanisms by which LSD1 control chromatin structure and gene transcription during Drosophila development and in cancer.
We aim to answer three main questions:
1) How does LSD1 activity control normal development and how does its alteration lead to tumorigenesis?
2) Which proteins and noncoding RNAs direct LSD1 targeting and to which genomic regions?
3) Which signaling pathways control LSD1 activity?
Identification of noncoding RNAs that bind dLSD1 in vivo
Regulation of dLsd1 by signaling pathways
Dissection of dLsd1 specific roles in regulating chromatin homeostasis and gene expression during development
- Wayne O. Miles, Julie M. J. Lepesant, Jessie Bourdeaux, Manuela Texier, Marc A. Kerenyi, Makoto Nakakido, Ryuji Hamamoto, Stuart H. Orkin, Nicholas J. Dyson, Luisa Di Stefano.
The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop
Molecular and Cellular Biology
2015 Dec Mol Cell Biol. 2015 Dec;35(24):4199-211. doi: 10.1128/MCB.00755-15.
- 2015 Jan Dietz KN, Di Stefano L, Maher RC, Zhu H, MacDonald ME, Gusella JF and Walker JA. The Drosophila Huntington’s disease gene ortholog dhtt influences chromatin regulation during development. Human Molecular Genetics 2015, Jan 15; 24(2): 330-45
- 2013 Jan Di Stefano L and Dyson N. The emerging roles for histone demethylases in the modulations of signaling pathways. Biomolecular Concepts. 2013; 4(1): 13–27
- 2011 Jul Di Stefano L and Dyson N. The complex roles of histone demethylases in vivo. Cell Cycle. 2011 Jul 1;10 (13): 2049-50.
- 2011 Jun Mulligan P, Yang F, Di Stefano L, Ji J, Nishikawa J, Wang Q, Kulkarni M, Najafi-Shoushtari H, Mostosvalsky R, Gygi S, Gill G, Dyson N and Näär A. A SIRT-LSD1 co-repressor complex regulating Notch target gene expression and development. Mol Cell. 2011 Jun 10;42(5):689-99.
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