Abstract:
:MyoD and NeuroD2, master regulators of myogenesis and neurogenesis, bind to a "shared" E-box sequence (CAGCTG) and a "private" sequence (CAGGTG or CAGATG, respectively). To determine whether private-site recognition is sufficient to confer lineage specification, we generated a MyoD mutant with the DNA-binding specificity of NeuroD2. This chimeric mutant gained binding to NeuroD2 private sites but maintained binding to a subset of MyoD-specific sites, activating part of both the muscle and neuronal programs. Sequence analysis revealed an enrichment for PBX/MEIS motifs at the subset of MyoD-specific sites bound by the chimera, and point mutations that prevent MyoD interaction with PBX/MEIS converted the chimera to a pure neurogenic factor. Therefore, redirecting MyoD binding from MyoD private sites to NeuroD2 private sites, despite preserved binding to the MyoD/NeuroD2 shared sites, is sufficient to change MyoD from a master regulator of myogenesis to a master regulator of neurogenesis.
journal_name
Cell Repjournal_title
Cell reportsauthors
Fong AP,Yao Z,Zhong JW,Johnson NM,Farr GH 3rd,Maves L,Tapscott SJdoi
10.1016/j.celrep.2015.02.055subject
Has Abstractpub_date
2015-03-31 00:00:00pages
1937-46issue
12issn
2211-1247pii
S2211-1247(15)00232-6journal_volume
10pub_type
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