Transcriptional Breakthroughs in Genetics

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    Groundwork Laid

  • Watson and Crick propose DNA structure

    This sets the stage for understanding how genetic information is copied and expressed.
  • The Central Dogma is proposed (Crick)

    Information flows DNA → RNA → Protein.
  • RNA polymerase first identified in bacteria

    Jerard Hurwitz helps isolate the enzyme that synthesizes RNA from a DNA template.
  • Discovery of messenger RNA (mRNA)

    Experiments reveal RNA carrying genetic information from DNA to ribosomes.
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    Decoding Transcription Mechanisms

  • Identification of transcription start sites

    Researchers map where RNA synthesis begins on DNA.
  • First sigma factor characterized

    Sigma subunits are shown to direct bacterial RNA polymerase to promoters.
  • Eukaryotic RNA polymerases I, II, III discovered

    Each dedicated to different RNA classes.
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    Promoters, Polymerases, and Splicing

  • First promoter sequences mapped in bacteria

    The –35 and –10 consensus sequences are defined experimentally.
  • Discovery of introns and RNA splicing

    Phillip Sharp and Richard Roberts independently discover split genes in eukaryotes.
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    Regulation and Enhancers

  • First enhancers discovered (SV40 enhancer)

    Shows that transcription can be activated from far upstream.
  • TATA-binding protein (TBP) identified

    Key component of TFIID; essential for Pol II transcription.
  • Chromatin remodeling complexes discovered

    Opens the field of transcriptional regulation through chromatin structure.
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    New Control Layers

  • CpG islands and DNA methylation linked to gene silencing

    DNA methylation becomes central to understanding transcriptional repression.
  • Mediator complex discovered

    Massive multiprotein complex that bridges transcription factors and RNA Pol II.
  • RNA interference (RNAi) discovered

    Fire and Mello show double-stranded RNA silences genes.
  • Human Genome Project reveals gene architecture

    Shows most of genome is noncoding; redefines transcriptional landscape.
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    Genome-wide Transcription Studies

  • Discovery of widespread noncoding RNAs (lncRNAs)

    Reveals transcription extends far beyond protein-coding genes.
  • Chromatin immunoprecipitation (ChIP-chip / ChIP-seq)

    Allows genome-wide mapping of transcription factor binding and histone marks.
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    Precision and Single-Cell Insights

  • CRISPR–Cas9 repurposed for gene regulation (CRISPRi/CRISPRa)

    Lets scientists turn transcription on or off at specific loci.
  • Single-cell RNA-seq emerges

    Reveals transcriptional differences at the level of single cells.
  • PRO-seq / GRO-seq reveal transcription pausing

    Shows pausing of RNA Pol II is a major regulatory mechanism.
  • Multiomics & AI modeling

    Integrates chromatin state, transcription factor binding, 3D genome architecture, and RNA output to predict gene expression with increasing accuracy.
  • Cryo-EM resolves high-resolution structures of transcription complexes

    Provides atomic details of Pol II initiation, pausing, and elongation.