Abstract
The nuclear protein CCCTC-binding factor (CTCF) contributes as an insulator to chromatin organization in animal genomes. Currently, our knowledge of its binding property is confined mainly to mammals. In this study, we identified CTCF homologs in extant jawless fishes and performed ChIP-seq for the CTCF protein in the Arctic lamprey. Our phylogenetic analysis suggests that the lamprey lineage experienced gene duplication that gave rise to its unique paralog, designated CTCF2, which is independent from the previously recognized duplication between CTCF and CTCFL. The ChIP-seq analysis detected comparable numbers of CTCF binding sites between lamprey, chicken, and human, and revealed that the lamprey CTCF protein binds to the two-part motif, consisting of core and upstream motifs previously reported for mammals. These findings suggest that this mode of CTCF binding was established in the last common ancestor of extant vertebrates (more than 500 million years ago). We analyzed CTCF binding inside Hox clusters, which revealed a reinforcement of CTCF binding in the region spanning Hox1-4 genes that is unique to lamprey. Our study provides not only biological insights into the antiquity of CTCF-based epigenomic regulation known in mammals but also a technical basis for comparative epigenomic studies encompassing the whole taxon Vertebrata.
Highlights
The CCCTC-binding factor (CTCF), containing the C2H2 Zn finger-type DNA binding domains, plays a pivotal role in chromatin organization as an insulator[1, 2]
In this study we identified two lamprey CTCF homologs, including CTCF2, which was duplicated in the lamprey lineage independently from the other gene duplication that gave rise to CTCFL
The sequence was extended by using RNA-seq data to obtain the transcript sequence of 5781 bp that encompasses the putative full-length open reading frame (ORF), which is markedly longer [1207 amino acids] than that of already reported orthologs [human, 727 aa (NCBI NP_0065561); fruitfly, 818 aa (NCBI NP_648109)]
Summary
The CCCTC-binding factor (CTCF), containing the C2H2 Zn finger-type DNA binding domains, plays a pivotal role in chromatin organization as an insulator[1, 2]. Whole genome sequencing and analysis was first carried out for the sea lamprey Petromyzon marinus and later for the Arctic lamprey Lethenteron camtschaticum (or Japanese lamprey L. japonicum)[14, 15] These genomic studies revealed its unique features, such as programmed genomic rearrangement and peculiar characters of protein-coding sequences associated with highly biased base composition towards increased GC-content[14, 16]. As these features could be influenced by epigenomic regulation through modifications of chromatin or DNA, it is crucial to investigate epigenomic regulation in this animal group. Focusing on Hox clusters, we compared CTCF binding patterns between lamprey and gnathostomes
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