Histone Methyltransferase SETD2 Is Required for Porcine Early Embryonic Development

Area of Science:

• Epigenetics
• Developmental Biology
• Molecular Biology

Background:

• SET domain-containing 2 (SETD2) methyltransferase modifies histone H3 lysine 36 (H3K36me2/me3).
• SETD2 regulates oocyte maturation and mouse embryonic development via H3K36me3.
• The role of SETD2 in porcine early embryonic development remains largely unknown.

Purpose of the Study:

• To investigate the specific substrate and function of SETD2 in porcine early embryonic development.
• To determine SETD2's role in H3K36me3 modification and its impact on embryonic development.

Main Methods:

• RNA interference (RNAi) via siRNA microinjection to knock down SETD2 expression.
• Immunofluorescence analysis to assess H3K36me2 and H3K36me3 levels.
• Evaluation of blastocyst rates, cell lineage allocation (ICM/TE), gene expression, and apoptosis.

Main Results:

• SETD2 preferentially catalyzes H3K36me3 modification in porcine embryos.
• SETD2 knockdown significantly reduced H3K36me3 levels but not H3K36me2.
• SETD2 deficiency decreased blastocyst rates, disrupted ICM/TE allocation, reduced key lineage gene expression, and increased apoptosis.

Conclusions:

• SETD2 is essential for porcine early embryonic development.
• SETD2's function is primarily mediated through H3K36me3 modification.
• SETD2 plays a critical role in blastocyst formation, cell lineage specification, and survival.