The Evolution of Epigenetic Regulators CTCF and BORIS/CTCFL in Amniotes

Timothy Hore, Janine Deakin, Jennifer Marshall Graves

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Abstract

CTCF is an essential, ubiquitously expressed DNA-binding protein responsible for insulator function, nuclear architecture, and transcriptional control within vertebrates. The gene CTCF was proposed to have duplicated in early mammals, giving rise to a paralogue called ‘‘brother of regulator of imprinted sites’’ (BORIS or CTCFL) with DNA binding capabilities similar to CTCF, but testis-specific expression in humans and mice. CTCF and BORIS have opposite regulatory effects on human cancertestis genes, the anti-apoptotic BAG1 gene, the insulin-like growth factor 2/H19 imprint control region (IGF2/H19 ICR), and show mutually exclusive expression in humans and mice, suggesting that they are antagonistic epigenetic regulators. We discovered orthologues of BORIS in at least two reptilian species and found traces of its sequence in the chicken genome, implying that the duplication giving rise to BORIS occurred much earlier than previously thought. We analysed the expression of CTCF and BORIS in a range of amniotes by conventional and quantitative PCR. BORIS, as well as CTCF, was found widely expressed in monotremes (platypus) and reptiles (bearded dragon), suggesting redundancy or cooperation between these genes in a common amniote ancestor. However, we discovered that BORIS expression was gonad-specific in marsupials (tammar wallaby) and eutherians (cattle), implying that a functional change occurred in BORIS during the early evolution of therian mammals. Since therians show imprinting of IGF2 but other vertebrate taxa do not, we speculate that CTCF and BORIS evolved specialised functions along with the evolution of imprinting at this and other loci, coinciding with the restriction of BORIS expression to the germline and potential antagonism with CTCF.
Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalPLoS Genetics
Volume4
Issue number8
DOIs
Publication statusPublished - 2008
Externally publishedYes

Fingerprint

Epigenomics
epigenetics
imprinting
genomic imprinting
gene
Genes
Vertebrates
Mammals
vertebrate
mammal
Platypus
genes
vertebrates
monotreme
mammals
Macropus eugenii
Macropodidae
functional change
DNA
Marsupialia

Cite this

Hore, Timothy ; Deakin, Janine ; Marshall Graves, Jennifer. / The Evolution of Epigenetic Regulators CTCF and BORIS/CTCFL in Amniotes. In: PLoS Genetics. 2008 ; Vol. 4, No. 8. pp. 1-11.
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The Evolution of Epigenetic Regulators CTCF and BORIS/CTCFL in Amniotes. / Hore, Timothy; Deakin, Janine; Marshall Graves, Jennifer.

In: PLoS Genetics, Vol. 4, No. 8, 2008, p. 1-11.

Research output: Contribution to journalArticle

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