Eukaryotic transcription initiation – TATA box binding: During assembly of the pre-initiation complex at a TATA-containing promoter, which general transcription factor first binds the TATA box to nucleate RNA polymerase II recruitment?

Introduction / Context:
Transcription initiation by RNA polymerase II requires an ordered assembly of general transcription factors (GTFs). The TATA box is a core promoter element in many, though not all, eukaryotic genes. Identifying the first factor that recognizes TATA is key to understanding pre-initiation complex architecture.

Given Data / Assumptions:

• TFIID contains the TATA-binding protein (TBP) plus TBP-associated factors (TAFs).
• Binding of TBP to the minor groove of the TATA box bends DNA and seeds PIC assembly.
• Subsequent factors (TFIIA, TFIIB, Pol II with TFIIF, then TFIIE/TFIIH) are recruited.

Concept / Approach:
The canonical order places TFIID (TBP) at the start, directly engaging TATA. TFIIA stabilizes TBP–DNA interaction; TFIIB bridges TBP–DNA with Pol II/TFIIF. TFIIH later provides helicase and kinase activities for promoter opening and CTD phosphorylation. Therefore, the “first binder” to the TATA sequence is TFIID through its TBP subunit.

Step-by-Step Solution:
Identify the element: TATA box. Recall that TBP (within TFIID) recognizes and binds TATA. Place TFIIA/TFIIB and Pol II recruitment after TBP binding. Select TFIID (via TBP) as the correct answer.

Verification / Alternative check:
Structural studies show TBP inducing an ~80° DNA bend at TATA before other GTFs load; TBP mutants disrupt PIC assembly at TATA promoters.

Why Other Options Are Wrong:
TFIIA/TFIIB bind after TBP; Pol II does not directly recognize TATA; TFIIE acts later with TFIIH to open the promoter.

Common Pitfalls:
Assuming all Pol II promoters are TATA-dependent; many are TATA-less and use TAF-mediated recognition of other core elements.

Final Answer:
TFIID (via TBP).