First published online June 25, 2007
Development 134, 1405e (2007)
© The Company of Biologists Limited
Novel developmental function for cohesin
The Runx1 transcription factor - an essential hematopoiesis regulator - is
involved in several leukaemia-causing chromosomal translocations. An important
route to understanding the pathology of such Runx-mediated cancers is to
elucidate what controls Runx expression or stability. Philip Crosier and
colleagues have now discovered, from a genetic screen in zebrafish for
positive regulators of runx1, that Rad21, a cohesin subunit,
regulates runx1 transcription in a dose-dependent manner. This
depends on cohesin, a protein complex that is required for sister chromatid
cohesion (p. 2639),
and is the first example of cohesin-dependent gene regulation in vertebrates.
In a series of genetic and morpholino-knockdown experiments, the authors show
that in zebrafish rad21 mutants, differentiated blood cells do not
form and runx3 and hematopoietic runx1 expression is lost.
Removing one copy of rad21 reduces runx1 and also downstream
proneural gene expression. Knocking down Smc3 - another cohesin subunit -
similarly reduces runx1 expression. Thus, the cohesin complex
regulates runx1 expression in zebrafish, but exactly how, awaits
future work.
Related articles in Development:
- Cohesin-dependent regulation of Runx genes
- Julia A. Horsfield, Sasha H. Anagnostou, Jimmy Kuang-Hsien Hu, Kitty Hsiao Yu Cho, Robert Geisler, Graham Lieschke, Kathryn E. Crosier, and Philip S. Crosier
Development 2007 134: 2639-2649.
[Abstract]
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