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← Theoretical A

Q8 — IGF2-H19 Imprinting and CTCF Loops

Theoretical A Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license
Gene Regulation: Eukaryotic & Epigenetics

Certain loci in the genome are influenced by epigenetic modifications, but understanding their precise mechanisms remains challenging. The IGF2-H19 locus serves as a well-known example, regulated by the methylation state of the imprinting control region (ICR). In addition to the two genes, this locus contains one enhancer and four CTCF-binding sites (CTCF is a DNA-binding protein), one of which serves as an ICR. A proposed model suggests that the spatial interaction among these elements underlies the regulatory mechanism governing the expression of IGF2 and H19. CTCF binding does not interrupt with the promoter function.

Panel A: paternal chromosome DNA drawn as a looping line, with IGF2 marked active (green arrow) and H19 inactive (red arrow), loops anchored by an orange CTCF/cohesin ring. Panel B: maternal chromosome with a different loop topology and both IGF2 and H19 shown with black (basal expression) arrows. Panel C: a simple diagram of a single CTCF/cohesin-anchored DNA loop. Panel D: a linear map of the locus showing IGF2 and H19 gene positions and CTCF-binding sites 1-4. Figure 1. A Paternal chromosome, IGF2 active (green arrow) and H19 inactive (red arrow). B Maternal chromosome, IGF2 and H19 basal expression (black arrows). Note that diagrams A and B reflect real physical distances and that intersection of two blue lines (representing DNA) reflects very close physical proximity of two DNA strands. C DNA loop formed by CTCF and cohesin. D IGF2-H19 locus with CTCF-binding sites 1-4 (CTCF-BS).

On your answer sheet, indicate “T” for true statements and “F” for false ones.

A. One CTCF-binding site can be involved in the formation of only one DNA loop.
B. ICR overlaps with CTCF binding site 2.
C. The enhancer is located between CTCF binding sites 3 and 4.
D. ICR methylation directly affects the expression of H19, independent of the enhancer.
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Question reproduced from IBO 2024, Theoretical Exam Part A, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)