ZNF146/OZF and ZNF507 target LINE-1 sequences

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Repetitive sequences, including transposable elements (TEs), constitute nearly half of the human genome.
• While active TEs require repression for genomic stability, fragmented TEs can regulate gene expression and genome organization.
• Understanding the proteins interacting with TEs is crucial for deciphering their regulatory roles.

Purpose of the Study:

• To identify proteins broadly enriched on human transposable elements using ChIP-seq data.
• To investigate the binding specificities and functions of ZNF146 and ZNF507 on LINE-1 elements.
• To explore the functional consequences of ZNF146 and ZNF507 disruption and their potential interactions.

Main Methods:

• Analysis of published ChIP-seq datasets to identify protein enrichment on TEs.
• CRISPR/Cas9-mediated gene disruption of ZNF146 and ZNF507 in HEK293 cells.
• RNA sequencing to assess gene expression changes post-disruption.
• Co-immunoprecipitation to identify protein-protein interactions.

Main Results:

• ZNF146 and ZNF507 were identified as proteins enriched on transposable elements, specifically binding to LINE-1 ORF2.
• ZNF146 binds to both old and young LINE-1 elements, whereas ZNF507 preferentially binds to young LINE-1 sequences.
• Disruption of ZNF507 led to modest changes in gene expression, and ZNF507 was found to physically interact with PRMT5.

Conclusions:

• ZNF146 and ZNF507 are novel proteins that bind to specific regions of LINE-1 elements.
• ZNF507's preferential binding to young LINE-1 elements and interaction with PRMT5 suggest a role in regulating LINE-1 activity and host gene expression.
• These findings contribute to understanding the regulatory roles of repetitive elements in the human genome.