During the last decades our view of the genome organization has changed. We 
moved from a linear view to a looped view of the genome. It is now well 
established that inter- and intra-connections occur between chromosomes and play 
a major role in gene regulations. These interconnections are mainly orchestrated 
by the CTCF protein, which is also known as the "master weaver" of the genome. 
Recent advances in sequencing and genome-wide studies revealed that CTCF binds 
to DNA at thousands of sites within the human genome, providing the possibility 
to form thousands of genomic connection hubs. Strikingly, two histone variants, 
namely H2A.Z and H3.3, strongly co-localize at CTCF binding sites. In this 
article, we will review the recent advances in CTCF biology and discuss the role 
of histone variants H2A.Z and H3.3 at CTCF binding sites.