James Kadonaga

About

James T. Kadonaga is a researcher focused on transcriptional regulation and chromatin dynamics. His work emphasizes understanding the mechanisms of gene regulation, particularly the regulation of transcription by RNA polymerase II. His research explores the diverse DNA elements within the RNA polymerase II core promoter, such as the TATA box, initiator (Inr), downstream core promoter element (DPE), motif ten element (MTE), and others, analyzing their roles at the DNA level, their interaction with transcription factors, and their function within biological networks. Kadonaga's lab has contributed to identifying and characterizing core promoter elements in Drosophila and humans, utilizing advanced techniques including machine learning models to predict promoter activity and element presence. His studies extend to the evolution of transcription-related factors like TRF2 and their influence on bilateria evolution. In addition to transcription regulation, Kadonaga investigates chromatin structure and its influence on gene expression. His team discovered the prenucleosome, a stable conformational isomer of the nucleosome associated with active promoters, which may facilitate transcription by recurring disruption of nucleosomes. His research also includes the identification of factors such as NDF, a nucleosome-destabilizing factor that promotes RNA polymerase II transcription through chromatin, and the Dsup protein from tardigrades, which binds to nucleosomes and protects DNA from…

Research topics

• Genetics
• Biology
• Artificial Intelligence
• Computational biology
• Cell biology
• Computer Science
• Nanotechnology
• Materials science

Selected publications

• The punctilious RNA polymerase II core promoter

  Genes & Development · 2017-07-01 · 156 citations

  reviewOpen accessSenior author

  The signals that direct the initiation of transcription ultimately converge at the core promoter, which is the gateway to transcription. Here we provide an overview of the RNA polymerase II core promoter in bilateria (bilaterally symmetric animals). The core promoter is diverse in terms of its composition and function yet is also punctilious, as it acts with strict rules and precision. We additionally describe an expanded view of the core promoter that comprises the classical DNA sequence motifs…

  PublisherOA PDFDOI

• The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals

  eLife · 2019-09-30 · 124 citations

  articleOpen accessSenior author

  Tardigrades, also known as water bears, are animals that can survive extreme conditions. The tardigrade Ramazzottius varieornatus contains a unique nuclear protein termed Dsup, for damage suppressor, which can increase the resistance of human cells to DNA damage under conditions, such as ionizing radiation or hydrogen peroxide treatment, that generate hydroxyl radicals. Here we find that R. varieornatus Dsup is a nucleosome-binding protein that protects chromatin from hydroxyl radicals. Moreover…

  PublisherDOI

• The human initiator is a distinct and abundant element that is precisely positioned in focused core promoters

  Genes & Development · 2017-01-01 · 95 citations

  articleOpen accessSenior author

  DNA sequence signals in the core promoter, such as the initiator (Inr), direct transcription initiation by RNA polymerase II. Here we show that the human Inr has the consensus of BBCA +1 BW at focused promoters in which transcription initiates at a single site or a narrow cluster of sites. The analysis of 7678 focused transcription start sites revealed 40% with a perfect match to the Inr and 16% with a single mismatch outside of the CA +1 core. TATA-like sequences are underrepresented in Inr pro…

  PublisherOA PDFDOI

• The RNA Polymerase II Core Promoter in <i>Drosophila</i>

  Genetics · 2019-03-06 · 93 citations

  reviewOpen accessSenior authorCorresponding

  Abstract Transcription by RNA polymerase II initiates at the core promoter, which is sometimes referred to as the “gateway to transcription.” Here, we describe the properties of the RNA polymerase II core promoter in Drosophila. The core promoter is at a strategic position in the expression of genes, as it is the site of convergence of the signals that lead to transcriptional activation. Importantly, core promoters are diverse in terms of their structure and function. They are composed of variou…

  PublisherOA PDFDOI

• The prenucleosome, a stable conformational isomer of the nucleosome

  Genes & Development · 2015-12-15 · 67 citations

  articleOpen accessSenior author

  Chromatin comprises nucleosomes as well as nonnucleosomal histone-DNA particles. Prenucleosomes are rapidly formed histone-DNA particles that can be converted into canonical nucleosomes by a motor protein such as ACF. Here we show that the prenucleosome is a stable conformational isomer of the nucleosome. It consists of a histone octamer associated with ∼ 80 base pair (bp) of DNA, which is located at a position that corresponds to the central 80 bp of a nucleosome core particle. Monomeric prenuc…

  PublisherOA PDFDOI

Recent grants

• Mechanisms of Eukaryotic Gene Regulation

  NIH · $7.5M · 2016–2031

• NIH Grant R01GM046995

  NIH · $2.6M · 2004

• Elucidation of Human TATA-less Transcription Networks

  NIH · $388k · 2016–2017

Frequent coauthors

• Robert Tjian

  California Institute for Regenerative Medicine

  34 shared

• Dmitry V. Fyodorov

  25 shared

• Chin Yan Lim

  Agency for Science, Technology and Research

  21 shared

• Alexandra Lusser

  Universität Innsbruck

  20 shared

• Karen M. Robinson

  Marquette University

  17 shared

• Làszlò Tora

  Centre National de la Recherche Scientifique

  16 shared

• Mariya M. Kurshakova

  Engelhardt Institute of Molecular Biology

  16 shared

• Е. Н. Набирочкина

  Institute of Gene Biology

  16 shared

Education

• Ph.D., Chemistry

  Harvard University

  1984

• S.B., Chemistry

  Massachusetts Institute of Technology

  1980

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