Advanced BiologyGene Expression and Regulation

Gene Regulation in Eukaryotes

Transcription factors bind promoters and enhancers; packing matters too: acetylating histones opens chromatin (more expression), methylating DNA usually closes it. These epigenetic marks can pass to daughter cells.

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Eukaryotes have no operons of the bacterial kind (Operons); each gene usually has its own promoter and its own controls. And their DNA is wound around proteins, so whether a gene can even be reached is part of the control.

  • Transcription factors: proteins that bind DNA. General transcription factors help RNA polymerase bind the promoter. Specific ones bind enhancers, control sequences that can be thousands of bases away; the DNA loops so they touch the promoter. Activators raise transcription; repressors lower it.
  • Chromatin packing: DNA winds around histone proteins into nucleosomes. Adding acetyl groups to histones loosens the packing, so genes are easier to read: more expression. Adding methyl groups to DNA (on cytosines, often near promoters) usually tightens packing and silences genes.
  • After transcription: alternative splicing, how long an mRNA lasts, and small RNAs (microRNAs) that block or destroy specific mRNAs all adjust how much protein is made.

Key idea

Eukaryotic genes are controlled by transcription factors at promoters and enhancers, and by packing: histone acetylation opens chromatin (more expression), DNA methylation usually closes it (less). These epigenetic marks can be copied to daughter cells, but they do not change the DNA sequence.
The double helix; in the nucleus it is wound around histones, tightly or loosely.

Why it works

Why do these marks act like switches? Histones are positively charged and DNA is negative, so they cling together. An acetyl group cancels part of a histone's positive charge, the grip loosens, and transcription factors can reach the DNA. Methylated DNA, on the other hand, attracts proteins that pack it tightly. When a cell divides, enzymes copy the methylation pattern onto the new strands, so the daughter cells keep the same genes on and off. That is how a liver cell's daughters stay liver cells.

Worked examples

Worked example: A drug that blocks deacetylation

A drug blocks the enzymes that remove acetyl groups from histones. What happens to genes that were packed tightly?
  1. Acetyl groups stay on, and more build up.
  2. Chromatin loosens.
  3. Transcription factors and RNA polymerase can reach more genes.

Answer: Many of those genes are expressed more.

Worked example: Deleting an enhancer

An enhancer 5,000 bases upstream of a gene is deleted. The promoter is untouched. What happens to transcription in cells that have the matching activator?
  1. The activator binds the enhancer and, by DNA looping, helps RNA polymerase at the promoter.
  2. With the enhancer gone, the activator has nowhere to bind.
  3. Only a low, basic level of transcription remains.

Answer: Transcription falls to a low level.

Common mistake

Thinking epigenetic changes alter the DNA sequence. Acetylation and methylation change how DNA is packed and read, not its bases: ATGC stays ATGC. That is why they can be reversed, and why identical genomes can behave differently.

Practice

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Sources and further reading

  • OpenStax, Biology 2e, 16.3 Eukaryotic Epigenetic Gene Regulation
  • OpenStax, Biology 2e, 16.4 Eukaryotic Transcriptional Gene Regulation
  • OpenStax, Biology 2e, 16.5 Eukaryotic Post-transcriptional Gene Regulation
  • NHGRI Talking Glossary: Epigenetics
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