Accepted_test

CTCF and the evolution of genome spatial organization
by Artem Nurislamov | Andrey Popov | Maria Gridina | Artem Shadskiy | Veniamin Fishman | Institute of Cytology and Genetics SB RAS, Novosibirsk State University | Institute of Cytology and Genetics SB RAS, Novosibirsk State University | Institute of Cytology and Genetics SB RAS | Institute of Cytology and Genetics SB RAS, Novosibirsk State University | Institute of Cytology and Genetics SB RAS, Novosibirsk State University
Abstract ID: 504
Event: BGRS-abstracts
Sections: [Sym 1] Section “Fundamental and applied 3D genomics”

The CCCTC-binding factor (CTCF) is a key insulator protein in bilaterian animals, exhibiting conserved structural features yet variable functions across different taxa. In vertebrates, CTCF facilitates chromatin loop formation via a cohesin/CTCF-dependent extrusion mechanism, crucial for the establishment of topologically associated domains (TADs). This mechanism, however, is absent in other bilaterian groups despite the conserved protein structure. This study aims to identify factors influencing the presence or absence of this loop extrusion mechanism in bilaterian animals.

We conducted an evolutionary analysis of CTCF amino acid sequences, with a particular focus on the N-terminal domain, which is highly variable and critical for chromatin loop formation in vertebrates. Multiple protein alignment techniques were employed to compare the evolutionary emergence of crucial amino acid motifs involved in cohesin interaction.

Our results revealed N-terminal domain sequences unique to jawed vertebrates, absent in jawless vertebrates and cephalochordates. We identified the KTYQR motif as a feature emerging specifically in jawed vertebrates, while the YXF motif was found across all studied bilaterian taxa except Trichinella spiralis, suggesting a loss of function in this species. The YXF motif is essential for chromatin loop formation in vertebrates, facilitating CTCF interaction with the loop extrusion complex.

In conclusion, the ability of vertebrate CTCF to participate in chromatin loop formation is influenced by both the presence of the YXF motif and other evolutionary factors, highlighting the complexity of chromatin organization mechanisms and the evolutionary divergence of CTCF functions in bilaterian animals.