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Publication : Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer.

First Author  Kondo T Year  2014
Journal  Dev Cell Volume  28
Issue  1 Pages  94-101
PubMed ID  24374176 Mgi Jnum  J:208353
Mgi Id  MGI:5562966 Doi  10.1016/j.devcel.2013.11.021
Citation  Kondo T, et al. (2014) Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer. Dev Cell 28(1):94-101
abstractText  Polycomb-group (PcG) proteins mediate repression of developmental regulators in a reversible manner, contributing to their spatiotemporally regulated expression. However, it is poorly understood how PcG-repressed genes are activated by developmental cues. Here, we used the mouse Meis2 gene as a model to identify a role of a tissue-specific enhancer in removing PcG from the promoter. Meis2 repression in early development depends on binding of RING1B, an essential E3 component of PcG, to its promoter, coupled with its association with another RING1B-binding site (RBS) at the 3' end of the Meis2 gene. During early midbrain development, a midbrain-specific enhancer (MBE) transiently associates with the promoter-RBS, forming a promoter-MBE-RBS tripartite interaction in a RING1-dependent manner. Subsequently, RING1B-bound RBS dissociates from the tripartite complex, leaving promoter-MBE engagement to activate Meis2 expression. This study therefore demonstrates that PcG and/or related factors play a role in Meis2 activation by regulating the topological transition of cis-regulatory elements.
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