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Published on: December 19, 2018
The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest
B A Firulli1, D B Hadzic, J R McDaid
1Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. firullia@UTHSCSA.edu
dHAND and eHAND transcription factors form homo- and heterodimers with multiple partners, influencing cardiac and limb development. This broad dimerization suggests a role in regulating gene transcription during embryogenesis.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- dHAND and eHAND are basic helix-loop-helix (bHLH) transcription factors crucial for embryonic development of cardiac and extraembryonic tissues.
- HAND genes, classified as class B bHLH proteins, typically form heterodimers with class A bHLH proteins like E-proteins for activity.
Purpose of the Study:
- To identify HAND-interacting proteins (HIPs) that regulate HAND gene activity.
- To investigate the dimerization capabilities of dHAND and eHAND with themselves and other bHLH proteins.
Main Methods:
- Yeast two-hybrid screening of a mouse embryonic library.
- Mammalian two-hybrid assays.
- Biochemical pull-down assays.
- Competition gel shift analysis.
Main Results:
- eHAND can form homodimers, contrary to typical bHLH gene behavior.
- dHAND and eHAND form both homo- and heterodimers in vivo.
- HAND proteins heterodimerize with Hairy-related transcription factors (HRT1-3).
- dHAND and eHAND negatively regulate the DNA binding of MyoD/E12 heterodimers, indicating a potential transcriptional inhibitory role.
Conclusions:
- dHAND and eHAND exhibit a broad dimerization profile, forming homo- and heterodimers with various bHLH partners.
- This extensive dimerization capability is likely a key mechanism by which HAND genes regulate gene transcription during development.
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