Curriculum
Module 09 · 70 min

Gene Expression & Chromatin

From nucleosomes to enhancers: how cells choose which genes to read.

CoreClinicalResearch
Topics

What this module covers

  • 01Nucleosomes, histone variants, histone modifications (Me, Ac, Ph, Ub)
  • 02DNA methylation: 5mC, 5hmC, imprinting, X-inactivation
  • 03Transcription factors, enhancers, super-enhancers, 3D genome (TADs)
  • 04RNA Pol II promoter-proximal pausing and release
  • 05Epigenetic memory and reprogramming (Yamanaka factors)
  • 06Cancer epigenetics: IDH, EZH2, DNMT3A, KMT2A
Deep dives

Lesson sub-pages

research 28 min· 3 refs
Enhancers, condensates, and the 3D genome
How distal regulatory elements find their target promoters across megabases — and why this re-frames cancer genomics.
Learning objectives

By the end of this module you will be able to

  • L01Explain how histone-mark patterns predict transcriptional state.
  • L02Connect a specific epigenetic mutation to a specific cancer or developmental syndrome.
  • L03Distinguish driver vs passenger epigenetic alterations.
Expected takeaways

What you should walk away believing

  • →Most disease-associated GWAS hits sit in non-coding enhancer regions, not in protein-coding sequence.
  • →Epigenetic therapies (DNMTi, HDACi, EZH2i) are now standard in selected hematologic malignancies.
  • →Pioneer transcription factors open chromatin — they are the entry points for cell-fate change.
Core summary

At the Core level

DNA is wrapped on histone octamers; modifications on histones and on DNA itself act as a regulatory code that recruits readers, writers, and erasers. Together they decide which genes a cell expresses now and remember next week. Three-dimensional folding into topologically associating domains determines which enhancers contact which promoters.

Myth vs reality

Common misconception

Claim

Lifestyle changes 'reprogram your epigenome'.

Reality

Diet and exercise alter some methylation marks, but claims of broad reprogramming are usually overstated; few clinical phenotypes are convincingly mediated by intentional epigenetic modulation outside oncology.

Evidence-graded claims

Claims, scored A–F

A
H3K4me3 marks active promoters
Established by genome-wide profiling.
B
Most non-coding GWAS variants act through gene-regulatory elements
Strongly supported by chromatin/eQTL colocalisation.
D
Phase separation alone explains transcription-factor function
Important emerging concept; specificity vs generality is debated.
Quiz

Check your understanding

Q1. IDH1/2 mutations produce:
Q2. Yamanaka reprogramming factors:
Flashcards

Lock it in

1 / 3
Front
Active vs repressed promoter marks?
Click to flip
Suggested reading

Primary literature

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