explain how gibberellin activates genes by causing the breakdown of DELLA protein repressors, which normally inhibit factors that promote transcription

Gene Control – Gibberellin (GA) Activation of Transcription

Learning objective

Explain how gibberellin (GA) activates genes by causing the breakdown of DELLA protein repressors, which normally inhibit transcription‑promoting factors.

Link to the Cambridge 9700 syllabus

• Topic 6 (Nucleic acids & protein synthesis) – 6.2: regulation of transcription (AO1, AO2).
• Topic 19 (Genetic technology) – 19.1: manipulation of growth pathways and use of molecular tools (AO1, AO2, AO3).
• Key concept Biochemical processes: conversion of a hormonal signal into a change in gene activity.
• Key concept Cells as the units of life: localisation of each component within the cell (nucleus, cytoplasm).

Key concepts (summary)

• Gibberellin (GA) – a diterpenoid plant hormone that promotes stem elongation, seed germination, flowering and fruit development.
• DELLA proteins – nuclear transcriptional repressors that bind and block GA‑responsive transcription factors (TFs). They act as “brakes” on growth.
• GID1 (GA‑INSENSITIVE DWARF1) – soluble nuclear GA receptor; belongs to the Hsp90‑like family.
• SCF^SLY1/GID2 complex – a SKP1‑Cullin‑F‑box (E3 ubiquitin ligase) that tags DELLA for destruction.
• 26S proteasome – multi‑subunit protease that recognises poly‑ubiquitin chains and degrades DELLA.
• Down‑stream transcription factors – PHYTOCHROME‑INTERACTING FACTORS (PIFs), BZR1, MYB and other GA‑responsive TFs that activate target genes once DELLA is removed.

Where the components are located

• GA enters the nucleus (and cytoplasm) by diffusion.
• GID1 and DELLA reside in the nucleus.
• SCF^SLY1/GID2 operates in both the nucleus and cytoplasm.
• The 26S proteasome is present in the nucleus and cytoplasm, allowing rapid removal of DELLA wherever it is tagged.

Step‑by‑step mechanism (transcriptional regulation)

1. GA perception – GA diffuses into the nucleus and binds GID1, forming a GA–GID1 complex.
   

   GA + GID1 ⇌ GA–GID1

2. DELLA recognition – Binding of GA causes a “lid‑closure” in GID1, creating a high‑affinity surface for the DELLA motif (Asp‑Glu‑Leu‑Leu‑Ala). The ternary GA–GID1–DELLA complex is assembled.
3. Recruitment of the SCF E3 ligase – The ternary complex attracts the SCF^SLY1/GID2 complex, which catalyses the attachment of a poly‑ubiquitin chain to lysine residues on DELLA.
   

   DELLA + Ubn →[SCFSLY1/GID2] DELLA–Ubn

4. Proteasomal degradation – Poly‑ubiquitinated DELLA is recognised by the 26S proteasome, unfolded, de‑ubiquitinated and hydrolysed into short peptides, permanently removing its repressive activity.
5. Transcription activation (the regulated step) – With DELLA gone, previously blocked transcription factors (e.g., PIFs, BZR1, MYB) can bind GA‑responsive promoters, recruit RNA polymerase II and initiate transcription of growth‑related genes.

Resulting cellular effects (genes switched on by GA)

• Expansins and other cell‑wall‑loosening enzymes – stem elongation.
• α‑amylase and other hydrolytic enzymes – seed germination.
• Flowering‑time regulators (e.g., FT, SOC1) – transition to reproductive phase.
• Fruit‑development proteins – cell division and expansion.

Biotechnological applications (Topic 19.1)

• GA‑responsive promoters are used to drive transgene expression only when GA levels are high, allowing conditional expression in crops.
• DELLA‑mutant dwarf varieties (e.g., “green‑revolution” wheat and rice) are created by reducing GA sensitivity or stabilising DELLA, producing shorter plants that are less prone to lodging.
• CRISPR/Cas‑mediated editing of GID1 or DELLA genes enables fine‑tuning of plant height, flowering time and stress tolerance.

Suggested practical (AO3 – experimental skills)

Objective: Demonstrate GA‑induced degradation of DELLA using a Western blot.

1. Grow Arabidopsis seedlings on agar plates; treat half with 10 µM GA₃, keep the other half as a control.
2. Harvest tissue at 0, 30, 60 and 120 min after treatment.
3. Extract total protein, run SDS‑PAGE and transfer to a membrane.
4. Probe with an anti‑DELLA antibody; use anti‑actin as a loading control.
5. Quantify band intensity with image analysis software. A progressive loss of the DELLA band in GA‑treated samples confirms hormone‑dependent proteolysis.

Optional deeper detail (for extension learners)

Advanced students may wish to explore the exact residues that line the GA‑binding pocket of GID1 (Leu‑147, Tyr‑161, Val‑182, Phe‑215) and the mechanistic steps of ubiquitin transfer (E1 → E2 → E3). This information is not required for the Cambridge examinations but provides insight into protein‑structure–function relationships.

Summary table

Key points to remember

• DELLA proteins act as growth “brakes”. GA removes these brakes by targeting DELLA for ubiquitin‑mediated proteolysis.
• The GA–GID1 interaction is reversible, allowing fine‑tuned control of signal intensity.
• Ubiquitin‑dependent degradation provides a rapid, essentially irreversible switch from repression to activation.
• Mutations that stabilise DELLA (e.g., loss of SCF function) produce dwarf phenotypes, illustrating the pathway’s importance for normal development.
• The cascade (hormone → receptor → E3 ligase → proteasome → transcription) exemplifies how a biochemical signal is converted into a change in gene expression – a core theme of the Cambridge A‑Level syllabus.