Discovery of novel TAF1 DNA binding domains in TFIID promoter recognition and gene transcription

Abstract

The central dogma of biology describes the basic flow of genetic information starting from DNA, which is converted to message RNA, then into functional proteins. This classical view provides a framework for how a cell can respond to its environment through changes in gene expression. While advances in DNA sequencing technology has greatly increased our knowledge of how this can occur on the genomic level, there are still a number of unanswered questions as to how that genetic information is accessed by transcriptional regulators. Controlling when a particular gene is transcribed is vital for cell survival and proliferation. Seminal work from the late 1980s and 1990s demonstrated the transcription factor IID (TFIID) complex as playing a critical role in regulating RNA polymerase II (RNAPII) transcriptional initiation. From these studies, we know TFIID is the first member of the core transcriptional machinery to recognize and bind gene promoter regions located at transcriptional start sites. Initial findings identified five proteins within the TFIID complex that possess DNA binding activities (TBP, TAF1, TAF2, TAF6, and TAF9). With the exception of TBP, little is known about their DNA binding surfaces, even though recent reports show the TAF components of TFIID are essential for promoter specificity. Presented here is the discovery of two DNA binding domains (DBDs) in TAF1, the largest TFIID subunit. This work identified and characterized two previously unknown DBDs, the winged helix (WH) located in the central DUF3591 domain and the evolutionarily conserved zinc knuckle (ZnK). The WH was exposed through structural studies of the TAF1/TAF7 heterodimer. ZnK was uncovered using bioinformatics as a strictly conserved motif in TAF1. Both DBDs play an imperative role in targeting TFIID to promoters of key cell cycle regulators. Understanding the critical binding regions of TAF proteins will further our knowledge of a fundamental biological process and give valuable insight into how transcription initiation can be regulated.