Biology subjects

Narducci, D. N.

Publications and source records attributed to Narducci, D. N..

2 recordsLinked to original sources

bioRxiv2024

Putative Looping Factor ZNF143/ZFP143 is an Essential Transcriptional Regulator with No Looping Function

Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143s role in this process and its function, either with or without CTCF, are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorially assess their looping function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function in mouse and human cells, and that it largely functions independently of CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor possessing an extremely stable chromatin residence time (>20 min) that regulates an important subset of mitochondrial and ribosomal genes.

genetics↗

bioRxiv2024

Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its ability to act as a chromatin organizer

Here we used a series of CTCF mutations to explore CTCFs relationship with chromatin and its contribution to gene regulation. CTCFs impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF proteins. Specifically, CTCFs signal strength is linked to changes in accessibility, and the ability to block cohesin is linked to its binding stability. Multivariate modelling reveals that both CTCF and accessibility contribute independently to cohesin binding and insulation, however CTCF signal strength has a stronger effect. CTCF and chromatin have a bidirectional relationship such that at CTCF sites, accessibility is reduced in a cohesin-dependent, mutant specific fashion. In addition, each mutant alters TF binding and accessibility in an indirect manner, changes which impart the most influence on rewiring transcriptional networks and the cells ability to differentiate. Collectively, the mutant perturbations provide a rich resource for determining CTCFs site-specific effects.

molecular biology↗