TY - JOUR
T1 - ASCL1 protein domains with distinct functions in neuronal differentiation and subtype specification
AU - Nakada, Yuji
AU - Martinez, Madison J.
AU - Johnson, Jane E.
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025/7
Y1 - 2025/7
N2 - ASCL1 is a neural basic helix-loop-helix (bHLH) transcription factor that plays essential roles during neural development, including neural differentiation and neuronal subtype specification. bHLH factors are defined by their motifs, including a basic region interacting with DNA and an HLH domain involved in protein-protein interactions. We previously defined specific regions within the bHLH domain of ASCL1 as important for its specific functions directing neuronal differentiation in the chick neural tube. Here, we build upon these findings to show how specific mutations within the basic region block DNA binding but not heterodimer formation with E-protein partners TCF3 (E12/E47) and TCF12 (HEB) yet have differential abilities to show dominant negative phenotypes. Additionally, truncating domains outside the bHLH define a nuclear localization signal, a requirement for the C-terminal acidic residues, and the non-essentiality of the N-terminal glutamine/alanine repeats. This structure/function analysis identifies functional domains for ASCL1 activity.
AB - ASCL1 is a neural basic helix-loop-helix (bHLH) transcription factor that plays essential roles during neural development, including neural differentiation and neuronal subtype specification. bHLH factors are defined by their motifs, including a basic region interacting with DNA and an HLH domain involved in protein-protein interactions. We previously defined specific regions within the bHLH domain of ASCL1 as important for its specific functions directing neuronal differentiation in the chick neural tube. Here, we build upon these findings to show how specific mutations within the basic region block DNA binding but not heterodimer formation with E-protein partners TCF3 (E12/E47) and TCF12 (HEB) yet have differential abilities to show dominant negative phenotypes. Additionally, truncating domains outside the bHLH define a nuclear localization signal, a requirement for the C-terminal acidic residues, and the non-essentiality of the N-terminal glutamine/alanine repeats. This structure/function analysis identifies functional domains for ASCL1 activity.
KW - ASCL1
KW - bHLH transcription factors
KW - Neurogenesis
KW - Neuronal specification
KW - Spinal cord development
UR - http://www.scopus.com/inward/record.url?scp=105002569801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=105002569801&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2025.04.001
DO - 10.1016/j.ydbio.2025.04.001
M3 - Article
C2 - 40187474
AN - SCOPUS:105002569801
SN - 0012-1606
VL - 523
SP - 32
EP - 42
JO - Developmental Biology
JF - Developmental Biology
ER -