A GATA-dependent right ventricular enhancer controls dHAND transcription in the developing heart

Area of Science:

• Developmental Biology
• Molecular Genetics
• Cardiovascular Research

Background:

• Vertebrate heart formation involves distinct progenitor populations for different chambers.
• Mechanisms specifying cardiac chamber lineages remain largely unknown.
• The transcription factor dHAND is crucial for heart development and neural crest formation.

Purpose of the Study:

• To elucidate the regulatory mechanisms controlling dHAND gene expression in cardiac development.
• To identify specific enhancers responsible for dHAND expression in different heart regions.
• To understand the role of GATA transcription factors in dHAND regulation during right ventricle development.

Main Methods:

• Utilized dHAND-lacZ reporter genes in transgenic mice to study gene regulation.
• Performed deletion analysis on cardiac-specific enhancers to pinpoint functional regions.
• Compared mouse and human regulatory sequences to identify conserved transcription factor binding sites.
• Mutated conserved GATA factor binding sites to assess their impact on transgene expression.

Main Results:

• Identified separate enhancers controlling cardiac and neural crest dHAND expression.
• Characterized a composite cardiac enhancer directing dHAND expression throughout heart development.
• Localized subregions within the enhancer responsible for right ventricle and outflow tract expression.
• Demonstrated that conserved GATA factor binding sites are essential for right ventricular dHAND expression.
• Established dHAND as a direct transcriptional target of GATA factors in right ventricle development.

Conclusions:

• Cardiac and neural crest expression of dHAND are regulated by distinct enhancers.
• GATA transcription factors directly regulate dHAND expression in the developing right ventricle.
• The findings suggest the involvement of coregulators in achieving right ventricular-specific gene expression through GATA factors.