Mutation c.-379 C>T in DGAT1 affects intramyocellular lipid content by altering MYOD1 binding affinity

Area of Science:

• Animal Genetics
• Molecular Biology
• Meat Science

Background:

• Intramuscular fat (IMF) content is crucial for pork taste quality.
• Diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triglyceride synthesis and fat deposition in skeletal muscle.
• The precise mechanisms regulating DGAT1 expression and its impact on IMF remain incompletely understood.

Purpose of the Study:

• To identify functional mutations in the DGAT1 gene that influence its expression and affect IMF deposition in pigs.
• To investigate the molecular mechanisms underlying the relationship between DGAT1 genetic variants and IMF content.

Main Methods:

• Comparative sequencing of DGAT1 in pigs with high and low IMF content.
• Genotyping and IMF content analysis in a cross-bred pig population.
• Gene expression analysis, luciferase reporter assays, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to study DGAT1 promoter activity and transcription factor binding.

Main Results:

• A novel SNP, c.-379 C>T, was identified in the DGAT1 promoter region.
• The c.-379 T allele was associated with significantly higher IMF content and DGAT1 expression compared to the C allele.
• Myogenic determination factor 1 (MYOD1) binds to the DGAT1 promoter with the c.-379 C allele, repressing transcription, but does not bind to the T allele, leading to increased DGAT1 expression and lipogenesis.

Conclusions:

• The SNP c.-379 C>T in the DGAT1 promoter is a functional mutation influencing IMF deposition in pigs.
• MYOD1's differential binding to DGAT1 promoter alleles explains the observed variations in DGAT1 expression and IMF content.
• This SNP serves as a valuable molecular marker for selective breeding to enhance pork IMF without negatively impacting other fat depots.