Sequence-specific transcription factors are critical mediators of cellular adaptation in response to both extracellular and intracellular cues. These rapidly changing transcriptional programs facilitate everything from cell fate decisions to stress responses, and the disruption of transcription factor function and/or expression is associated with disease states including developmental disorders, neurologic disorders, and cancer. We take a chemical-genetic approach to rapidly degrade endogenous transcription factor proteins, which allows us to identify changes in transcription networks, chromatin states, and genome-wide transcription factor occupancy within the first hours of transcription factor removal. We leverage the rapid kinetics of this approach to address fundamental questions in the transcription field including how transcription factors are influenced by and exert influence over the chromatin landscape, how multiple sequence-specific transcription factors cooperate to fine-tune gene expression, how enhancer activity controls promoter activation, and how disruption of these processes can promote tumor development.

Bomber ML, Wang J, Liu Q, Barnett KR, Layden HM, Hodges E, Stengel KR*, Hiebert SW*. (2023) Human SMARCA5 is continuously required to maintain nucleosome spacing. Mol Cell. 83(4): P507-522. PMID: 36630954 *corresponding author

Previewed in: Xu JJ and Viny AD (2023) Till SMARCA5 loss do nucleosomes part. Mol Cell. 83(4): P500-501.

Zhang S, Wang J, Liu Q, McDonald WH, Bomber ML, Layden HM, Ellis J, Borinstein SC, Hiebert SW*, Stengel KR*. (2022) PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and RNA polymerase pause release at select target genes. Mol Cell. 82(23):4428-4442. PMID: 36395771. *corresponding author

Layden HM, Eleuteri NA, Hiebert SW, Stengel KR. (2021) A protocol for rapid degradation of endogenous transcription factors in mammalian cells and identification of direct regulatory targets. STAR Protoc. 2(2): 100530. PMID: 34041503.

Stengel KR*, Ellis JD, Spielman C, Bomber M, Hiebert SW*. (2021) Definition of a Small Core Transcriptional Circuit Regulated by AML1-ETO. Mol. Cell. 81(3): 530-545. PMID: 33382982 *corresponding author

Previewed in: Lu, C. (2021) Decoding the function of an oncogenic transcription factor: finding the first responders. Mol. Cell. 81(3): 418-420. PMID: 33545056.