Table of Contents

REVIEWS

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Epigenetic modulators provide a path to understanding disease and therapeutic opportunity
- Madison A. Honer,
- Benjamin I. Ferman,
- Zach H. Gray,
- Elena A. Bondarenko,
- and Johnathan R. Whetstine
Genes Dev. June 1, 2024 38: 473-503; Published in Advance June 24, 2024, doi:10.1101/gad.351444.123
OPEN ACCESS ARTICLE
In this review, Honer et al. unravel our mechanistic understanding of how DNA and chromatin modifiers, like writers, erasers, readers, and remodelers, function and contribute to human disease. They further highlight recent advances in both monotherapies and combination therapeutic approaches that target these epigenetic modulators to combat various diseases.
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RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity
- Rosa Luna,
- Belén Gómez-González,
- and Andrés Aguilera
Genes Dev. June 1, 2024 38: 504-527; Published in Advance July 10, 2024, doi:10.1101/gad.351853.124
OPEN ACCESS ARTICLE
R-loops, RNA–DNA hybrid structures, are often a source of genome instability, requiring the cell to use various mechanisms to prevent or alleviate them. In this review, Luna et al. discuss the origin of R-loops and describe how several factors involved in RNA biogenesis, processing, export, and metabolism play a secondary role in R-loop suppression or resolution.

RESEARCH COMMUNICATION

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Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer
- Norman Zhu,
- W. Eric Rogers,
- David K. Heidary,
- and Tom Huxford
Genes Dev. June 1, 2024 38: 528-535; Published in Advance July 3, 2024, doi:10.1101/gad.351892.124
In this study, Zhu et al. describe the structure of the IκBζ in complex with NF-κB's p50 homodimer and dissect the domain functions involved in their folding stability and binding affinity and specificity. They also show that IκBζ interacts with p50:RelA heterodimers, not only providing insight into the structural rearrangements that are required for the complex's association with target DNA but also suggesting that IκBζ serves as a transcriptional coregulator for both RelA- and NFκB-dependent gene expression.

RESEARCH PAPERS

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Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50–IκBζ pathway
- Allison E. Daly,
- George Yeh,
- Sofia Soltero,
- and Stephen T. Smale
Genes Dev. June 1, 2024 38: 536-553; Published in Advance June 25, 2024, doi:10.1101/gad.351630.124
OPEN ACCESS ARTICLE
In this study, Daly et al. report a p50- and IκBζ-dependent coregulatory axis that controls the expression of a subset of codependent inflammatory genes in activated macrophages. IκBζ binds NF-κB-primed accessible chromatin and, in concert with RelA:p50 heterodimers, promotes differential, immunoregulatory transcriptional programs in response to TLR4 and TNFR stimulation.
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ChAHP2 and ChAHP control diverse retrotransposons by complementary activities
- Josip Ahel,
- Aparna Pandey,
- Michaela Schwaiger,
- Fabio Mohn,
- Anja Basters,
- Georg Kempf,
- Aude Andriollo,
- Lucas Kaaij,
- Daniel Hess,
- and Marc Bühler
Genes Dev. June 1, 2024 38: 554-568; Published in Advance July 3, 2024, doi:10.1101/gad.351769.124
OPEN ACCESS ARTICLE
In this study, Ahel et al. describe a novel protein complex, ChAHP2, involved in transposon silencing, that is predominantly targeted to ERVs and LINEs via HP1β-mediated binding of H3K9 trimethylated histones. Analogous to but distinct from the SINE-repressive ChAHP complex, the ChAHP2 complex suppresses ERVs and LINE1 elements, with both complexes functioning complementarily to bring about efficient retrotransposon repression.
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Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy
- Li Guan,
- Vignesh Viswanathan,
- Yuyan Jiang,
- Sivakamasundari Vijayakumar,
- Hongbin Cao,
- Junfei Zhao,
- Deana Rae Crystal Colburg,
- Patrick Neuhöfer,
- Yiru Zhang,
- Jinglong Wang,
- Yu Xu,
- Eyiwunmi E. Laseinde,
- Rachel Hildebrand,
- Mobeen Rahman,
- Richard Frock,
- Christina Kong,
- Philip A. Beachy,
- Steven Artandi,
- and Quynh-Thu Le
Genes Dev. June 1, 2024 38: 569-582; Published in Advance July 12, 2024, doi:10.1101/gad.351577.124
In this study, Guan et al. discover a telomerase reverse transcriptase (TERT)-expressing progenitor population in the salivary gland with enhanced proliferation and survival capacity after exposure to radiation. The work posits a role for TERT in providing resistance to radiation-induced oxidative stress and cell damage, with implications for tissue regeneration strategies in cancers, such as head and neck cancer, where radiotherapy is used.

CORRIGENDUM

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Corrigendum: The evolutionary turnover of recombination hot spots contributes to speciation in mice
- Fatima Smagulova,
- Kevin Brick,
- Yongmei Pu,
- R. Daniel Camerini-Otero,
- and Galina V. Petukhova
Genes Dev. June 1, 2024 38: 583; doi:10.1101/gad.352049.124
OPEN ACCESS ARTICLE

REVIEWS

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity

RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity

RESEARCH COMMUNICATION

Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer

RESEARCH PAPERS

Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50–IκBζ pathway

ChAHP2 and ChAHP control diverse retrotransposons by complementary activities

Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy

CORRIGENDUM

Corrigendum: The evolutionary turnover of recombination hot spots contributes to speciation in mice

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