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Research: Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain
- James L. Shepherdson,
- David M. Granas,
- Jie Li,
- Zara Shariff,
- Stephen P. Plassmeyer,
- Alex S. Holehouse,
- Michael A. White,
- and Barak A. Cohen
Genome Res. October 2024 34: 1540-1552; Published in Advance September 25, 2024, doi:10.1101/gr.279415.124
...superimposed on a predicted structure of the CRX homeodomain in complex with DNA. (A) Various views of residues 38–104 of an AlphaFold predicted structure of CRX aligned to a crystal structure of Drosophila paired in complex with DNA (PDB 1FJL) (Wilson et al. 1995). For each view, a cartoon ribbon model...
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Research: Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors
- James L. Shepherdson,
- Ryan Z. Friedman,
- Yiqiao Zheng,
- Chi Sun,
- Inez Y. Oh,
- David M. Granas,
- Barak A. Cohen,
- Shiming Chen,
- and Michael A. White
Genome Res. February 2024 34: 243-255; Published in Advance February 14, 2024, doi:10.1101/gr.278133.123
..., or with cooperatively interacting transcriptional cofactors. The consequences of these disrupted interactions could vary across thousands of different cis-regulatory elements (CREs) in ways that depend on their DNA sequence composition. Although the DNA-binding specificity of CRX is well characterized (Corbo et al...
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Method: The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects
- Maureen Pittman,
- Kihyun Lee,
- Franco Felix,
- Yu Huang,
- Adrienne Lam,
- Mauro W. Costa,
- Deepak Srivastava,
- and Katherine S. Pollard
Genome Res. February 2026 36: 330-347; Published in Advance December 12, 2025, doi:10.1101/gr.281141.125
...of these gene pairs with additional modifier genes (Supplemental Table S14). For example, the predicted digenic pair CFAP46–DNAH11 was found by GCOD in higher-order interactions among probands with septation defects, in one case a gene quad including cilia gene CROCC2 and regulator of DNA demethylation PROSER1...
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Research: Developmental transcriptomics in Pristionchus reveals the environmental responsiveness of a plasticity gene-regulatory network
- Shelley Reich,
- Tobias Loschko,
- Julie Jung,
- Samantha Nestel,
- Ralf J. Sommer,
- and Michael S. Werner
Genome Res. July 2025 35: 1560-1573; Published in Advance June 9, 2025, doi:10.1101/gr.279783.124
...and difficulties in laboratory rearing.The nematode Pristionchus pacificus was introduced as a model system for studying developmental plasticity in 2010 (Bento et al. 2010). Similar to Caenorhabditis elegans, P. pacificus has four larval stages (J1–J4), although the first stage remains enclosed in the egg...
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Research: Optical genome mapping identifies rare structural variants in neural tube defects
- Nikhil S. Sahajpal,
- Jane Dean,
- Benjamin Hilton,
- Timothy Fee,
- Cindy Skinner,
- Alex Hastie,
- Barbara R. DuPont,
- Alka Chaubey,
- Michael J. Friez,
- and Roger E. Stevenson
Genome Res. April 2025 35: 798-809; Published in Advance March 19, 2025, doi:10.1101/gr.279318.124
...and clinicopathological findings in NTD cases and mothersOptical mappingOGM was performed following the manufacturer's protocol (Bionano Genomics, San Diego, CA, USA) as described previously (Sahajpal et al. 2023b). Briefly, ultra-high-molecular-weight DNA was isolated using a nanodisc-based isolation method, which...
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Research: ISWI1 complex proteins facilitate developmental genome editing in Paramecium
- Aditi Singh,
- Lilia Häußermann,
- Christiane Emmerich,
- Emily Nischwitz,
- Brandon K.B. Seah,
- Falk Butter,
- Mariusz Nowacki,
- and Estienne C. Swart
Genome Res. January 2025 35: 93-108; Published in Advance November 14, 2024, doi:10.1101/gr.278402.123
...are similar to those observed for ISWI1 knockdown. We thus propose that a complex comprising ISWI1 and either or both ICOPa and ICOPb are needed for Paramecium’s precise editing.Chromatin's underlying subunit, the nucleosome, comprises ∼146 bp of DNA wrapped around an octamer of histone proteins (Kornberg...
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Research: Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells
- Jennifer A. Urban,
- Daniel Ringwalt,
- John M. Urban,
- Wingel Xue,
- Ryan Gleason,
- Keji Zhao,
- and Xin Chen
Genome Res. January 2026 36: 83-101; Published in Advance December 10, 2025, doi:10.1101/gr.280809.125
...Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells Jennifer A. Urban1, Daniel Ringwalt1, John M. Urban2,3, Wingel Xue1,5, Ryan Gleason1, Keji Zhao4 and Xin Chen1,2 1Department of Biology, The Johns Hopkins University...
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Resource: A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz,
- Vivien Schoonenberg,
- Rachel Mullner,
- Albert Fradera-Sola,
- Susanne Zimbelmann,
- Joshua J Smith,
- and Falk Butter
Genome Res. January 28, 2026 gr.281000.125; Published in Advance January 28, 2026, doi:10.1101/gr.281000.125
...-4)PPs) 47 and cis-syn cyclobutane pyrimidine dimers (Spivak 2015), repaired by NER. Cisplatin (CPT) 48 induces covalent bonds between base pairs on different DNA strands referred to as interstrand 49 crosslinks (ICLs) (Huang et al. 1995); this damage is often repaired by NER, however there is 50 a cell...
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Research: Characterization of DNA methylation reader proteins in Arabidopsis thaliana
- Jonathan Cahn,
- James P.B. Lloyd,
- Ino D. Karemaker,
- Pascal W.T.C. Jansen,
- Jahnvi Pflueger,
- Owen Duncan,
- Jakob Petereit,
- Ozren Bogdanovic,
- A. Harvey Millar,
- Michiel Vermeulen,
- and Ryan Lister
Genome Res. December 2024 34: 2229-2243; Published in Advance December 4, 2024, doi:10.1101/gr.279379.124
.../or record transcriptional activity of their underlying genetic sequences (Bird 2007). One such modification is cytosine DNA methylation (mC), the covalent bond of a methyl group (–CH3) to the fifth carbon of cytosine bases. In plants, mC can occur in three DNA sequence contexts: CG, CHG, and CHH (H = A, C...
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Mini-Review: Revisiting models of enhancer–promoter communication in gene regulation
- Gilad Barshad and
- Charles G. Danko
Genome Res. June 2025 35: 1277-1286; doi:10.1101/gr.278389.123
...of this discussion revolves around the architecture of enhancers’ interactions with their cognate promoters. For many years, the prevailing model proposed that enhancers and promoters come into close physical proximity in the nucleus, creating “loops” composed of the DNA polymer connecting them (Choi and Engel 1988...

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