GATE BT 2023 • Q40 MSQ • 2 Marks

Section 3: Genetics, Cellular and Molecular Biology

DNA replication, transcription, translation

Subtopic: Fundamentals of DNA replication, transcription, translation

Question Statement:

Methylation of CpG islands near the promoter of a gene can inhibit transcription by

Options:

  • (A) preventing RNA polymerase binding
  • (B) facilitating repressor binding
  • (C) facilitating heterochromatin formation
  • (D) inducing euchromatin formation

Official Answer Key:

A;B;C

Step-by-Step Solution & Explanation

### **Official Solution & Concept Analysis (GATE BT 2023 Q.40)** **1. Governing Concept**: - **Topic**: Epigenetics & Transcriptional Repression via DNA Methylation - **CpG island methylation** (addition of a methyl group to the 5-position of cytosine by DNA methyltransferases, DNMTs) in promoter regions silences gene transcription through distinct molecular mechanisms: 1. **Steric Hindrance**: Directly blocks the binding of transcription factors whose consensus motifs contain CpG sequences (e.g., AP-2, c-Myc, CREB). 2. **Recruitment of Methyl-CpG-Binding Domain (MBD) Proteins**: Proteins like **MeCP2**, MBD1, and MBD2 specifically recognize and bind 5-methylcytosine. 3. **Histone Deacetylase (HDAC) Recruitment**: MBD proteins form corepressor complexes with histone deacetylases and histone methyltransferases, de-acetylating histones and compacting chromatin into repressive heterochromatin. **2. Option Analysis**: - **Option (A) [Directly blocking the binding of transcription factors] is CORRECT**: Methylated cytosines sterically and electrostatically prevent sequence-specific transcription factor engagement. - **Option (B) [Recruiting methyl-CpG-binding proteins (MBPs)] is CORRECT**: MBPs bind methylated CpG dinucleotides with high affinity. - **Option (C) [Recruiting histone deacetylases (HDACs)] is CORRECT**: MBD proteins partner with Sin3A/NuRD complexes containing HDAC1/2 to deacetylate histones and repress transcription. - **Option (D) [Promoting histone acetylation] is INCORRECT**: Histone acetylation activates transcription; methylation recruits deacetylases to remove acetyl marks. **3. Final Answer**: - **Correct Options**: **A, B, C**

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