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.