Roles of NIPBL in maintenance of genome stability.

A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. The present article overviews the critical and regulatory roles of NIBPL in cohesion loading on chromotin and in gene expression and transcriptional signaling. We explore molecular mechanisms by which NIPBL recruits endogenous histone deacetylase (HDAC) to induce histone deacetylation and influence multi-dimensions of genome, through which NIPBL "hop" movement in chromatin regulates gene expression and alters genome folding. NIPBL regulates the process of CTCF and cohesion into chromatin loops and topologically associated domains, binding of cohesion and H3K4mes3 through interaction among promoters and enhancers. HP1 recruits NIPBL to DNA damage site through RNF8/RNF168 ubiquitylation pathway. NIPBL contributes to regulation of genome-controlled gene expression through the influence of cohesin in chromosome structure. NIPBL interacts with cohesin and then increases transcriptional activities of REC8 promoter, leading to up-regulation of gene expression. NIPBL movement among chromosomal loops regulates gene expression through dynamic alterations of genome organization. Thus, we expect a new and deep insight to understand dynamics of chromosome and explore potential strategies of therapiesc on basis of NIPBL.