Conversion of MyoD to a neurogenic factor: binding site specificity determines lineage.

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 Rep

journal_title

Cell reports

authors

Fong AP,Yao Z,Zhong JW,Johnson NM,Farr GH 3rd,Maves L,Tapscott SJ

doi

10.1016/j.celrep.2015.02.055

subject

Has Abstract

pub_date

2015-03-31 00:00:00

pages

1937-46

issue

12

issn

2211-1247

pii

S2211-1247(15)00232-6

journal_volume

10

pub_type

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