The Igf2 gene is expressed from the paternal parent but not from the maternal parent. An ICR is located between the H19 and Igf2 genes. If a mutation eliminated this ICR, how would it affect the expression of the Igf2 gene?

Question

The Igf2 gene is expressed from the paternal parent but not from the maternal parent. An ICR is located between the H19 and Igf2 genes. If a mutation eliminated this ICR, how would it affect the expression of the Igf2 gene?

BlackTom AI · Accepted Answer

CTCF binding at the imprinting control region (ICR) between H19 and Igf2 determines which allele is expressed. Relevant concepts: genomic imprinting, differential DNA methylation, the ICR acting as a CTCF-dependent insulator, and enhancer-promoter interactions for H19 and Igf2.

Step-by-step reasoning:
1) Normal allele-specific states: On the maternal chromosome the ICR is unmethylated and binds CTCF. CTCF blocks shared downstream enhancers from interacting with the Igf2 promoter, so Igf2 is off (silenced) maternally while H19 is expressed. On the paternal chromosome the ICR is methylated, preventing CTCF binding; the enhancers can access the Igf2 promoter so paternal Igf2 is expressed while H19 is silenced by methylation.
2) If the ICR is eliminated by mutation, the CTCF binding site is removed on the maternal chromosome. Without the insulator, there is no barrier to enhancer-promoter contact on the maternal allele.
3) Consequence: Enhancers that normally activate Igf2 on the paternal side can now also activate the maternal Igf2, causing biallelic (both parental) expression of Igf2.
4) The paternal allele remains expressed as before because its activation depends on absence of CTCF (methylated ICR) and that situation is unchanged by deletion of the ICR; deletion does not restore repression on the paternal side.

Why correct answer is correct: Removing the ICR abolishes the maternal insulator function, allowing maternal Igf2 expression while leaving paternal expression intact—hence “It would not affect the expression of the paternal allele, but the maternal allele would be expressed.”

Why other options are incorrect:
- Option 2 reverses parent effects incorrectly; maternal is normally silent because of ICR, so deletion would activate it, not leave it unchanged.
- Options 3 and 4 predict inhibition, but deletion of the insulator removes repression on the maternal allele (not cause inhibition), and paternal expression is not inhibited by losing the ICR.

Final confirmation: The correct choice is “It would not affect the expression of the paternal allele, but the maternal allele would be expressed.”

The Igf2 gene is expressed from the paternal parent but not from the maternal parent. An ICR is located between the H19 and Igf2 genes. If a mutation eliminated this ICR, how would it affect the expression of the Igf2 gene?单项选择题

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