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Dev Cell March 16, 2010; 18 (3): 450-62.

BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning.

Sakano D , Kato A , Parikh N , McKnight K , Terry D , Stefanovic B , Kato Y .

Although the Notch signaling pathway is one of the most intensely studied intracellular signaling pathways, the mechanisms by which Notch signaling regulates transcription remain incompletely understood. Here, we report that B cell leukemia/lymphoma 6 (BCL6), a transcriptional repressor, is a Notch-associated factor. BCL6 is necessary to maintain the expression of Pitx2 in the left lateral plate mesoderm during the patterning of left-right asymmetry in Xenopus embryos. For this process, BCL6 forms a complex with BCL6 corepressor (BCoR) on the promoters of selected Notch target genes such as enhancer of split related 1. BCL6 also inhibits the transcription of these genes by competing for the Notch1 intracellular domain, preventing the coactivator Mastermind-like1 (MAM1) from binding. These results define a mechanism restricting Notch-activated transcription to cell-type-appropriate subsets of target genes, and elucidate its relevance in vivo during left-right asymmetric development.

PubMed ID: 20230751
PMC ID: PMC2841049
Article link: Dev Cell
Grant support: [+]
Genes referenced: bcl6 bcor gal.2 hes4 hes5.1 maml1 nodal1 notch1 pitx2 tubb2b
Morpholinos: bcl6 MO1 hes5.1 MO1 notch1 MO1

Article Images: [+] show captions
Adachi, 1999, Pubmed [+]

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