Questions: Chromatin Remodeling and Gene Accessibility

Question 1

A cancer researcher finds that a tumor suppressor gene has a completely normal DNA sequence but is not being expressed. Which mechanism could explain this?

• A. A frameshift mutation in the coding region
• B. Nucleosomes occluding the gene's promoter, blocking transcription factor access
• C. A deletion of the gene's exons
• D. A stop codon introduced by a point mutation

Answer: (B)

Chromatin remodeling explains how a gene with an intact DNA sequence can be silenced. If nucleosomes are positioned over the promoter, transcription factors cannot bind even though the sequence is correct — this is exactly the mechanism implicated in ~20% of human cancers through SWI/SNF mutations. The other answers all require changes to the DNA sequence itself, which the premise rules out. Chromatin accessibility is a regulatory layer independent of sequence.

Question 2

A cell needs to rapidly activate a gene in response to a signaling event. What characteristic of chromatin remodeling makes it suited for this role?

• A. It permanently modifies the DNA sequence to make the promoter more accessible
• B. It is a slow, gradual process that ensures careful control over gene activation
• C. It is dynamic and reversible, allowing rapid changes to chromatin accessibility
• D. It works by degrading histones at active gene promoters

Answer: (C)

The key feature of chromatin remodeling is that it is tunable and reversible — a gene can be opened or closed depending on which remodeling complexes are recruited, and the state can change rapidly in response to signals. This is what makes it suited for responsive regulation. It does not modify DNA sequence (that would be mutation), it is not inherently slow, and histone exchange is a distinct mechanism from degradation.

Question 3

Two cells with identical DNA sequences — such as a neuron and a liver cell — can express entirely different genes because their chromatin landscapes differ.

• T. True
• F. False

Answer: True

This is the central implication of chromatin remodeling. DNA sequence is identical in every cell of the body; what differs is which regions of chromatin are accessible. Remodeling complexes, responding to cell-type-specific signals, open different promoters in different cell types, producing dramatically different transcriptomes from identical genomes. Chromatin state, not sequence alone, determines which genes are actually read.

Question 4

ATP-dependent chromatin-remodeling complexes change gene accessibility by permanently altering the DNA sequence around gene promoters.

• T. True
• F. False

Answer: False

Remodeling complexes use ATP hydrolysis to physically reposition, slide, or eject nucleosomes — they do not change the DNA sequence. The accessibility they create is reversible: nucleosomes can be repositioned back over a promoter to silence the gene again. This is fundamentally different from DNA methylation or mutations, both of which modify the DNA itself. The distinction matters because reversibility is what allows cells to dynamically regulate gene expression.

Question 5

Why does a mutation in a SWI/SNF chromatin-remodeling subunit lead to tumor suppressor gene silencing even when that gene's DNA sequence is intact?

Model answer: SWI/SNF remodeling complexes are responsible for opening chromatin at gene promoters so transcription factors can bind. If a subunit is mutated and the complex cannot function, it fails to expose the tumor suppressor gene's promoter — the gene is silenced even though its sequence is undamaged. The cell loses the brake on proliferation not because the brake pedal is broken, but because a physical barrier is blocking access to it.

This cancer mechanism occurs in ~20% of tumors. The genome has two separable levels: sequence information and packaging (accessibility) that determines whether the sequence is used. Both can fail independently. SWI/SNF mutations don't destroy the gene; they prevent the cell from accessing it. Recognizing that gene expression failures can result from packaging defects — not just sequence mutations — is a major conceptual shift in understanding cancer biology.