Fast-acting chemical tools to delineate causality in transcriptional control

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

(2020) Rati Verma et al.   MOLECULAR CELL

Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer

(2020) Emily J. Faivre et al.   NATURE

Single-cell multimodal omics: the power of many

(2020) Chenxu Zhu et al.   NATURE METHODS

Absolute Quantification of Transcription Factors Reveals Principles of Gene Regulation in Erythropoiesis

(2020) Mark A. Gillespie et al.   MOLECULAR CELL

Selective Mediator dependence of cell-type-specifying transcription

(2020) Martin G. Jaeger et al.   NATURE GENETICS

Selective targeting of BD1 and BD2 of the BET proteins in cancer and immuno-inflammation

(2020) Omer Gilan et al.   SCIENCE

Phosphorylation-Inducing Chimeric Small Molecules

(2020) Sachini U. Siriwardena et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation

(2020) Michael Tellier et al.   NUCLEIC ACIDS RESEARCH

A super-sensitive auxin-inducible degron system with an engineered auxin-TIR1 pair

(2020) Kohei Nishimura et al.   NUCLEIC ACIDS RESEARCH

Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II

(2020) Pabitra K. Parua et al.   Nature Communications

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

(2020) Behnam Nabet et al.   Nature Communications

Definition of a small core transcriptional circuit regulated by AML1-ETO

(2020) Kristy R. Stengel et al.   MOLECULAR CELL

Advancements in the Development of non-BET Bromodomain Chemical Probes

(2019) Michael A. Clegg et al.   ChemMedChem

Visualizing DNA folding and RNA in embryos at single-cell resolution

(2019) Leslie J. Mateo et al.   NATURE

A chemical toolbox for the study of bromodomains and epigenetic signaling

(2019) Qin Wu et al.   Nature Communications

Single-Molecule Nanoscopy Elucidates RNA Polymerase II Transcription at Single Genes in Live Cells

(2019) Jieru Li et al.   CELL

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

(2019) William Farnaby et al.   Nature Chemical Biology

Bromodomains: a new target class for drug development

(2019) Andrea G. Cochran et al.   NATURE REVIEWS DRUG DISCOVERY

Pharmacological Modulation of Transcriptional Coregulators in Cancer

(2019) Timothy R. Bishop et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Chemical genomics reveals histone deacetylases are required for core regulatory transcription

(2019) Berkley E. Gryder et al.   Nature Communications

CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation

(2019) Malgorzata Krajewska et al.   Nature Communications

NASC-seq monitors RNA synthesis in single cells

(2019) Gert-Jan Hendriks et al.   Nature Communications

CUT&Tag for efficient epigenomic profiling of small samples and single cells

(2019) Hatice S. Kaya-Okur et al.   Nature Communications

A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers

(2019) Laila El Khattabi et al.   CELL

An efficient auxin-inducible degron system with low basal degradation in human cells

(2019) Shiqian Li et al.   NATURE METHODS

Nascent RNA analyses: tracking transcription and its regulation

(2019) Erin M. Wissink et al.   NATURE REVIEWS GENETICS

A 50 year history of technologies that drove discovery in eukaryotic transcription regulation

(2019) John T. Lis   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery

(2019) Anna M. Chiarella et al.   NATURE BIOTECHNOLOGY

Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma

(2019) Berkley E. Gryder et al.   NATURE GENETICS

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

The pause-initiation limit restricts transcription activation in human cells

(2019) Saskia Gressel et al.   Nature Communications

Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

(2019) Sayumi Yamazoe et al.   JOURNAL OF MEDICINAL CHEMISTRY

Analog-sensitive cell line identifies cellular substrates of CDK9

(2019) Tim-Michael Decker et al.   Oncotarget

Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome

(2018) Brian T. Weinert et al.   CELL

Visualizing transcription factor dynamics in living cells

(2018) Zhe Liu et al.   JOURNAL OF CELL BIOLOGY

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet et al.   Nature Chemical Biology

Kinase inhibitors: the road ahead

(2018) Fleur M. Ferguson et al.   NATURE REVIEWS DRUG DISCOVERY

Chemically induced proximity in biology and medicine

(2018) Benjamin Z. Stanton et al.   SCIENCE

SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis

(2018) Matthias Muhar et al.   SCIENCE

Structure of activated transcription complex Pol II–DSIF–PAF–SPT6

(2018) Seychelle M. Vos et al.   NATURE

Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation

(2018) Ryan Raisner et al.   Cell Reports

Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel–Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7

(2018) Vittoria Zoppi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Transcriptional Burst Initiation and Polymerase Pause Release Are Key Control Points of Transcriptional Regulation

(2018) Caroline R. Bartman et al.   MOLECULAR CELL

Genomic encoding of transcriptional burst kinetics

(2018) Anton J. M. Larsson et al.   NATURE

A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation

(2018) Brittany C. Michel et al.   NATURE CELL BIOLOGY

Role of the pre-initiation complex in Mediator recruitment and dynamics

(2018) Elisabeth R Knoll et al.   eLife

FKBP Ligands—Where We Are and Where to Go?

(2018) Jürgen M. Kolos et al.   Frontiers in Pharmacology

GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP)

(2017) F. Anthony Romero et al.   JOURNAL OF MEDICINAL CHEMISTRY

Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes

(2017) Carlo Baejen et al.   MOLECULAR CELL

Genome-wide Single-Molecule Footprinting Reveals High RNA Polymerase II Turnover at Paused Promoters

(2017) Arnaud R. Krebs et al.   MOLECULAR CELL

BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment

(2017) Georg E. Winter et al.   MOLECULAR CELL

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

(2017) Loren M. Lasko et al.   NATURE

Transcription control by the ENL YEATS domain in acute leukaemia

(2017) Michael A. Erb et al.   NATURE

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

(2017) Calla M Olson et al.   Nature Chemical Biology

Paused RNA polymerase II inhibits new transcriptional initiation

(2017) Wanqing Shao et al.   NATURE GENETICS

TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin

(2017) Erik L Miller et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Rapid and reversible epigenome editing by endogenous chromatin regulators

(2017) Simon M. G. Braun et al.   Nature Communications

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors

(2017) Jayme L. Dahlin et al.   Nature Communications

TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin

(2017) Erik L Miller et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo

(2017) Natalia Petrenko et al.   eLife

CDK9-dependent RNA polymerase II pausing controls transcription initiation

(2017) Saskia Gressel et al.   eLife

An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites

(2017) Peter J Skene et al.   eLife

P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates

(2016) Miriam Sansó et al.   GENES & DEVELOPMENT

Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor

(2016) Laetitia J. Martin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

(2016) Tinghu Zhang et al.   Nature Chemical Biology

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

(2016) Anja F Hohmann et al.   Nature Chemical Biology

Dynamics of BAF–Polycomb complex opposition on heterochromatin in normal and oncogenic states

(2016) Cigall Kadoch et al.   NATURE GENETICS

Complex transcriptional modulation with orthogonal and inducible dCas9 regulators

(2016) Yuchen Gao et al.   NATURE METHODS

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

(2016) Kanak Raina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TT-seq maps the human transient transcriptome

(2016) Björn Schwalb et al.   SCIENCE

Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation

(2016) B. A. Gibson et al.   SCIENCE

Optogenetic Control of Protein Function: From Intracellular Processes to Tissue Morphogenesis

(2016) Giorgia Guglielmi et al.   TRENDS IN CELL BIOLOGY

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis -Regulatory Elements

(2016) Anand S. Bhagwat et al.   Cell Reports

Rapid Protein Depletion in Human Cells by Auxin-Inducible Degron Tagging with Short Homology Donors

(2016) Toyoaki Natsume et al.   Cell Reports

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies

(2015) Bhavatarini Vangamudi et al.   CANCER RESEARCH

Native Elongating Transcript Sequencing Reveals Human Transcriptional Activity at Nucleotide Resolution

(2015) Andreas Mayer et al.   CELL

Mammalian NET-Seq Reveals Genome-wide Nascent Transcription Coupled to RNA Processing

(2015) Takayuki Nojima et al.   CELL

Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction

(2015) Bethany E. Schaffer et al.   Cell Metabolism

Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition

(2015) Natalie H. Theodoulou et al.   JOURNAL OF MEDICINAL CHEMISTRY

ChIP-nexus enables improved detection of in vivo transcription factor binding footprints

(2015) Qiye He et al.   NATURE BIOTECHNOLOGY

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems

(2015) Tetsushi Sakuma et al.   Nature Protocols

CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II–transcribed genes

(2015) Clélia Laitem et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II–transcribed genes

(2015) Clélia Laitem et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance

(2015) O. Fedorov et al.   Science Advances

Looping Back to Leap Forward: Transcription Enters a New Era

(2014) Michael Levine et al.   CELL

Subcellular optogenetics - controlling signaling and single-cell behavior

(2014) W. K. A. Karunarathne et al.   JOURNAL OF CELL SCIENCE

TFIIH Phosphorylation of the Pol II CTD Stimulates Mediator Dissociation from the Preinitiation Complex and Promoter Escape

(2014) Koon Ho Wong et al.   MOLECULAR CELL

Chemistry: Chemical con artists foil drug discovery

(2014) Jonathan Baell et al.   NATURE

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

Histone core modifications regulating nucleosome structure and dynamics

(2014) Peter Tessarz et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond

(2014) Eric Verdin et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes

(2014) M. G. J. Baud et al.   SCIENCE

Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

(2014) Ignacio Izeddin et al.   eLife

Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons

(2014) Iris Jonkers et al.   eLife

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

Signaling Pathways Differentially Affect RNA Polymerase II Initiation, Pausing, and Elongation Rate in Cells

(2013) Charles G. Danko et al.   MOLECULAR CELL

Precise Maps of RNA Polymerase Reveal How Promoters Direct Initiation and Pausing

(2013) H. Kwak et al.   SCIENCE

An expanded tool kit for the auxin-inducible degron system in budding yeast

(2013) Magdalena Morawska et al.   YEAST

Dynamics and Memory of Heterochromatin in Living Cells

(2012) Nathaniel A. Hathaway et al.   CELL

Bioorthogonal Profiling of Protein Methylation Using Azido Derivative of S-Adenosyl-l-methionine

(2012) Kabirul Islam et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction

(2012) Dennis L. Buckley et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Profiling Genome-Wide Chromatin Methylation with Engineered Posttranslation Apparatus within Living Cells

(2012) Rui Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Labeling Substrates of Protein Arginine Methyltransferase with Engineered Enzymes and MatchedS-Adenosyl-l-methionine Analogues

(2011) Rui Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Comprehensive analysis of kinase inhibitor selectivity

(2011) Mindy I Davis et al.   NATURE BIOTECHNOLOGY

Histone modification: cause or cog?

(2011) Steven Henikoff et al.   TRENDS IN GENETICS

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

The promise of optogenetics in cell biology: interrogating molecular circuits in space and time

(2010) Jared E Toettcher et al.   NATURE METHODS

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

An auxin-based degron system for the rapid depletion of proteins in nonplant cells

(2009) Kohei Nishimura et al.   NATURE METHODS

The Anchor-Away Technique: Rapid, Conditional Establishment of Yeast Mutant Phenotypes

(2008) Hirohito Haruki et al.   MOLECULAR CELL

Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters

(2008) Leighton J. Core et al.   SCIENCE