Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Transposons (mobile genetic elements) significantly influence genome evolution and gene regulation.
• SETMAR, a protein methylase, evolved from a transposase after integration of the Hsmar1 transposon.
• The SETMAR protein possesses both DNA-binding and methylase activities.

Purpose of the Study:

• To investigate the regulatory role of SETMAR in gene expression.
• To determine the contribution of SETMAR's DNA-binding domain and methylase activity to its function.
• To elucidate SETMAR's involvement in primate-specific regulatory networks.

Main Methods:

• Overexpression of SETMAR in human cells.
• Analysis of gene expression changes using quantitative methods (e.g., RNA-Seq).
• Comparison of wild-type SETMAR with a methylase-deficient mutant.

Main Results:

• SETMAR overexpression (modest) altered the expression of approximately 1500 genes (>2-fold change), with 65% upregulated.
• Affected genes were enriched in KEGG Pathways in Cancer and included developmental transcription factors.
• A methylase-deficient SETMAR mutant affected significantly fewer genes, primarily downregulating them without significant pathway enrichment.

Conclusions:

• SETMAR's DNA-binding domain targets it to transposon remnants, mediating gene expression regulation.
• SETMAR's methylase activity is crucial for its regulatory function and impact on gene expression.
• SETMAR appears to be a component of an anthropoid primate-specific regulatory network involving transposon-associated genes.