ZNF143 is a regulator of chromatin loop

Zi Wen, Zhi-Tao Huang, Ran Zhang, Cheng Peng

It is known that transcription factor ZNF143 frequently co-binds with CTCF-Cohesin complex in the anchor regions of chromatin loops. However, there is currently no genome-wide experiment to explore the functional roles of ZNF143 in chromatin loops. In this work, we used both computational and experimental analyses to investigate the regulatory effect of ZNF143 on chromatin loops. By jointly analyzing the ZNF143 and CTCF motifs underlying the isolated ZNF143-binding sites, ZNF143-CTCF co-binding sites and ZNF143-CTCF-RAD21 co-binding sites, our result shows that the ZNF143-CTCF-RAD21 co-binding sites are enriched with CTCF motifs but depleted of Znf143 motifs, implying that the CTCF but not ZNF143 may directly binds to the genome and thus ZNF143 may act as a cofactor instead of pioneer factor of ZNF143-CTCF-Cohesin complex. To explore the regulatory effect of ZNF143 on chromatin loops, we conducted siRNA experiment to knock down the expression level of ZNF143 in HEK293T cell line, and then performed in situ Hi-C on the negative control and ZNF143-silenced HEK293T cells. Comparison shows that the majority of chromatin loops are lost or at least weakened in the ZNF143-silenced HEK293T cells. However, a small proportion of chromatin loops are gained or strengthened, indicating the complicated roles of ZNF143 reduction in regulating chromatin loops. To further validate the loop analyses, we thoroughly investigated the chromatin loop changes between negative control and ZNF143-silenced cells by using aggregate peak analysis. The calculation shows that the lost and gained chromatin loops do undergo loop strength changes after ZNF143 silencing. Altogether, our work shows that ZNF143 can regulate chromatin loops by acting as a cofactor of CTCF-Cohesin complex, and knocking down ZNF143 expression level mainly eliminates or destabilizes chromatin loops.