Illustration of RNA polymerase II, SAGA, and TFIID complexes regulating gene expression inside a cell nucleus.

Decoding Gene Regulation: How Coactivator Complexes Orchestrate RNA Polymerase II Transcription

Beau Callahan in Science & Nature August 2025 • 5 min read.

"Unraveling the global role of SAGA and TFIID complexes in the intricate process of RNA polymerase II transcription and their implications for gene expression."

The synthesis of messenger RNA (mRNA) is vital. RNA polymerase II (Pol II)-mediated transcription stands as a highly regulated process. It determines cellular function and cell identity through the accurate synthesis of mRNAs. This regulation, particularly at the initiation stage, is a key mechanism to control gene expression.

Initiation requires the basal transcription machinery, which includes Pol II and general transcription factors (GTFs). This machinery nucleates the pre-initiation complex (PIC) on gene promoters. TFIID, comprising the TATA-box binding protein (TBP) and TBP-associated factors (TAFs), is the first GTF to bind promoter sequences. Once bound, GTFs correctly position Pol II relative to the transcription start site (TSS), facilitating the transition to productive elongation.

The compact structure of chromatin presents a barrier to PIC formation. Other transcription factors are required to modulate the chromatin landscape near promoters. These are coactivators, recruited to gene promoters by gene-specific activators. Coactivators possess activities that facilitate transcription, including chromatin remodeling, histone modification, and adaptor functions. While some coactivator complexes regulate specific genes, others, like the Mediator complex, have a more global role. This article will summarize recent insights into the global roles of TFIID and SAGA (Spt-Ada-Gcn5-acetyltransferase) in Pol II transcription in yeast. It will also discuss potential global functions for other coactivators and similar mechanisms in metazoans.

SAGA and TFIID: Key Players in Pol II Transcription

Illustration of RNA polymerase II, SAGA, and TFIID complexes regulating gene expression inside a cell nucleus.

An extensively characterized coactivator is the evolutionarily conserved SAGA complex, which is organized into distinct functional and structural modules. SAGA activates transcription through histone modifying activities, such as acetylation and deubiquitination, and by recruiting TBP to promoters. Early genome-wide analyses of SAGA function in Pol II transcription in budding yeast revealed that deletion of the TBP-interacting subunit Spt3 decreased the steady-state RNA levels of approximately 10% of genes by more than twofold. Meanwhile, 90% of the genes were affected upon conditional depletion of the TFIID subunit Taf1, which is also involved in TBP-recruitment to promoters.

The initial study cautiously concluded that “TFIID and SAGA make overlapping contributions to the expression of all genes.” However, the classification of genes as either SAGA-dominated or TFIID-dominated became oversimplified, categorizing each gene as dependent exclusively on one or the other coactivator. It was shown that SAGA-dominated genes were highly enriched in stress-regulated genes containing consensus TATA elements in their core promoters, while TFIID-dominated genes tended to be more constitutively expressed and lack a strong consensus TATA.

The Mediator complex is an integral part of the basal transcription machinery, required for nearly all Pol II mediated transcription.
SAGA activates transcription through histone modifying activities and by recruiting TBP to promoters.
TFIID directly contacts DNA and interacts with other components of the basal transcription machinery.

The analysis of the genome-wide localization of SAGA by chromatin immunoprecipitation (ChIP) indicated that SAGA is recruited to a limited subset of genes, in agreement with its requirement for the expression of only ~10% of the yeast genome. However, subsequent comparison of localization and expression studies showed a weak correlation between chromatin binding sites and transcriptional effects. Indeed, several studies revealed that a global decrease in Pol II transcription is compensated by a simultaneous and global decrease in mRNA decay, thereby buffering steady-state mRNA levels. The use of improved methodologies was highly warranted to re-examine the role of SAGA and TFIID in Pol II transcription.

Final Thoughts: A Symphony of Regulation

As a global role in Pol II transcription is now proposed for three different coactivator complexes (Mediator, SAGA and TFIID), it is tempting to speculate that other coactivators might also have a broader function than anticipated. Although SAGA, TFIID and Mediator can be considered as general cofactors for Pol II in yeast, it does not imply that each complex makes equal contributions to the expression of every individual gene. Delving into the intricacies of how these coactivators function provides a richer understanding of gene regulation and its impact on cellular processes.

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This article is based on research published under:

DOI-LINK: 10.1080/21541264.2018.1521214, Alternate LINK

Title: Global Role For Coactivator Complexes In Rna Polymerase Ii Transcription

Subject: Genetics

Journal: Transcription

Publisher: Informa UK Limited

Authors: Veronique Fischer, Kenny Schumacher, Laszlo Tora, Didier Devys

Published: 2018-10-09

Everything You Need To Know

What are the primary coactivator complexes involved in RNA Polymerase II transcription, and what is their significance?

The primary coactivator complexes discussed are SAGA (Spt-Ada-Gcn5-acetyltransferase) and TFIID. SAGA activates transcription through histone modifying activities, such as acetylation and deubiquitination, and by recruiting TBP to promoters. TFIID, which includes the TATA-box binding protein (TBP) and TBP-associated factors (TAFs), is the first general transcription factor to bind promoter sequences and correctly positions Pol II relative to the transcription start site (TSS). These complexes are significant because they play crucial roles in modulating the chromatin landscape and facilitating the formation of the pre-initiation complex (PIC), ultimately influencing gene expression and cellular functions. The Mediator complex is also an integral part of the basal transcription machinery, required for nearly all Pol II mediated transcription.

How do SAGA and TFIID influence gene expression differently in yeast, particularly in relation to TATA elements and gene regulation?

SAGA and TFIID exhibit different preferences in gene regulation. Studies have indicated that SAGA-dominated genes are highly enriched in stress-regulated genes containing consensus TATA elements in their core promoters. In contrast, TFIID-dominated genes tend to be more constitutively expressed and lack a strong consensus TATA. This suggests that SAGA is more involved in regulating genes that respond to environmental changes, while TFIID is crucial for the consistent expression of genes required for basic cellular functions. The initial classification of genes as exclusively SAGA-dominated or TFIID-dominated turned out to be oversimplified.

What methods have been used to study the genome-wide localization of SAGA, and what challenges have researchers faced in correlating its location with its transcriptional effects?

Chromatin immunoprecipitation (ChIP) has been used to study the genome-wide localization of SAGA. However, researchers have faced challenges in correlating chromatin binding sites with transcriptional effects. Initial studies suggested SAGA is recruited to a limited subset of genes, aligning with its requirement for only a small portion of the yeast genome. However, subsequent comparisons of localization and expression studies revealed a weak correlation between where SAGA binds and its actual impact on transcription. A global decrease in Pol II transcription can be compensated by a simultaneous and global decrease in mRNA decay, thereby buffering steady-state mRNA levels.

Beyond SAGA and TFIID, how might other coactivator complexes contribute to the regulation of RNA Polymerase II transcription?

Given that Mediator, SAGA, and TFIID have been identified as general cofactors for Pol II in yeast, it is reasonable to consider that other coactivators might also have broader functions than initially anticipated. While these complexes don't necessarily contribute equally to every gene's expression, they collectively ensure precise control over gene regulation. The possibility of additional coactivators having a global role suggests a complex, interconnected network of regulatory factors, each contributing uniquely to the symphony of gene expression.

What is the role of RNA Polymerase II (Pol II) in gene expression, and why is the initiation stage of transcription particularly important?

RNA Polymerase II (Pol II) is responsible for synthesizing messenger RNA (mRNA), which is essential for gene expression. The initiation stage of transcription is particularly important because it determines cellular function and cell identity through the accurate synthesis of mRNAs. The initiation process requires the basal transcription machinery, including Pol II and general transcription factors (GTFs), to nucleate the pre-initiation complex (PIC) on gene promoters. Precise regulation at this stage ensures that genes are expressed at the right time and in the right amounts, controlling various cellular processes.