ZNF143 is a regulator of chromatin loop

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Transcription factor ZNF143 is known to co-bind with the CTCF-Cohesin complex at chromatin loop anchor regions.
• The precise genome-wide functional roles of ZNF143 in regulating chromatin loops remain unexplored.

Purpose of the Study:

• To investigate the regulatory effect of ZNF143 on chromatin loops using computational and experimental approaches.
• To determine whether ZNF143 acts as a pioneer factor or a cofactor in the ZNF143-CTCF-Cohesin complex.

Main Methods:

• Joint analysis of ZNF143 and CTCF motifs at various binding sites (ZNF143, ZNF143-CTCF, ZNF143-CTCF-RAD21).
• siRNA-mediated knockdown of ZNF143 in HEK293T cells.
• In situ Hi-C and aggregate peak analysis to assess changes in chromatin loops.

Main Results:

• ZNF143-CTCF-RAD21 co-binding sites are enriched for CTCF motifs but depleted of ZNF143 motifs, suggesting CTCF is the primary binder and ZNF143 acts as a cofactor.
• ZNF143 knockdown significantly reduces or eliminates many chromatin loops, while a small subset is gained or strengthened.
• Aggregate peak analysis confirmed significant changes in loop strength upon ZNF143 silencing.

Conclusions:

• ZNF143 regulates chromatin loops by functioning as a cofactor for the CTCF-Cohesin complex.
• Reduced ZNF143 levels primarily lead to the elimination or destabilization of chromatin loops, highlighting its importance in maintaining genome architecture.