General summary

The Taatjes lab investigates the molecular mechanisms by which the human transcription machinery functions and is regulated.  Proper regulation of gene expression is fundamental to every major physiological process, and changes in gene expression patterns are hallmarks of human development and disease.  Consequently, the questions that we address are fundamentally important and have broad relevance to human health. Read more

Mediator kinases and CDK8-Mediator

Our lab and others have shown that a four-subunit CDK8 module can reversibly associate with the 26-subunit Mediator complex. The CDK8 module is 600 kDa in size and consists of MED12, MED13, CDK8, and CCNC. The CDK8 module acts as a kinase (CDK8) and likely functions on its own, as well as when associated with Mediator, as the so-called “CDK8-Mediator” complex.   Read more

Transcription Factors and PIC function 

Mediator is a common target of DNA-binding transcription factors (TFs) and also interacts with various components within the Pre-Initiation Complex (PIC), which consists of TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, Mediator itself, and pol II.  Read more

Structure and function of the RNA polymerase II transcription machinery

The Pre-Initiation Complex (PIC), which consists of Mediator, TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and RNA polymerase II (pol II), governs the expression of all protein-coding and most non-coding RNA genes in the human genome and is over 4.0 MDa in size.  Read more

p53 and aging

The p53 transcription factor is best known as a tumor suppressor but also plays fundamental roles in aging, metabolism, and stem cell biology.  A naturally occurring p53 isoform, called Δ40p53 (or ΔNp53), causes accelerated aging in mice when expressed together with WTp53.  Read more