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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M Riley,
- Randa Elsayed,
- Mark D Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C Nelson
Genome Res. March 4, 2026 gr.280838.125; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
...to mediate 57 consistent phenotypic outcomes there must also be consistent regulation of such genes by 58 cis-regulatory modules (CRMs). CRMs consist of clusters of transcription factor binding sites 59 (TFBSs) that regulate the expression of target genes through collective or competitive binding 60...
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Research: Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
- Kevin Moyung,
- Yulong Li,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. January 2026 36: 115-128; Published in Advance December 9, 2025, doi:10.1101/gr.279637.124
...mechanisms and support the robustness of our findings.Our work opens other avenues for future studies. Many yeast TFs act in condition-specific ways, and the deletion of such TFs under log-phase growth in rich medium in some cases has no significant transcriptional effects. Therefore, one future direction...
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Method: Long-read reconstruction of many diverse haplotypes with devider
- Jim Shaw,
- Christina Boucher,
- Yun William Yu,
- Noelle Noyes,
- and Heng Li
Genome Res. December 2025 35: 2637-2649; Published in Advance September 23, 2025, doi:10.1101/gr.280510.125
...55421, USA Corresponding author: jshaw@ds.dfci.harvard.eduAbstractReconstructing exact haplotypes is important when sequencing a mixture of similar sequences. Long-read sequencing can connect distant alleles to disentangle similar haplotypes, but handling sequencing errors requires specialized...
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Method: A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis
- Daijun Zhang,
- Ren Qi,
- Xun Lan,
- and Bin Liu
Genome Res. August 2025 35: 1794-1808; Published in Advance July 14, 2025, doi:10.1101/gr.280281.124
..., confirming the necessity and effectiveness of each module. This indicates that adding H&E image data offers essential phenotypic information, which improves the slice alignment task and increases the effectiveness of multilayer joint analysis. The reconstruction of the cellular landscape and the insights...
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Perspective: Notable challenges posed by long-read sequencing for the study of transcriptional diversity and genome annotation
- Carolina Monzó,
- Adam Frankish,
- and Ana Conesa
Genome Res. April 2025 35: 583-592; Published in Advance March 3, 2025, doi:10.1101/gr.279865.124
...-specific, real RNA molecules: (i) the need to acknowledge this fraction of the transcriptome as different from the condition-specific transcriptional program and develop bioinformatics methods that distinguish these authentic molecules from technological artifacts to study their biological relevance, and (ii...
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Research: Epigenetic drift score captures directional methylation variability and links aging to transcriptional, metabolic, and genetic alterations
- Xiu Fan,
- Qili Qian,
- Wenran Li,
- Tianzi Liu,
- Changqing Zeng,
- Peilin Jia,
- Huandong Lin,
- Xin Gao,
- Li Jin,
- Mingfeng Xia,
- Sijia Wang,
- and Fan Liu
Genome Res. October 2025 35: 2173-2188; Published in Advance August 1, 2025, doi:10.1101/gr.280155.124
...decreased variability (negative drift). Integration with single-cell RNA-seq data demonstrates that positive drift-CpGs are associated with increased transcriptional variability and upregulation in specific cell types, whereas negative drift-CpGs exhibit the opposite effect. We develop epigenetic drift...
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Research: Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations
- Irene Mei,
- Susanne Nichterwitz,
- Melanie Leboeuf,
- Jik Nijssen,
- Isadora Lenoel,
- Dirk Repsilber,
- Christian S. Lobsiger,
- and Eva Hedlund
Genome Res. September 2025 35: 1975-1991; Published in Advance July 17, 2025, doi:10.1101/gr.279501.124
...) that innervate skeletal muscles. However, certain MN groups including ocular MNs, are relatively resilient. To reveal key drivers of resilience versus vulnerability in ALS, we investigate the transcriptional dynamics of four distinct MN populations in SOD1G93A ALS mice using LCM-seq and single...
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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
..., Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110, USA Corresponding author: cohen@wustl.eduAbstractThe transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause...
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Research: Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution
- Chris Papadopoulos,
- Isabelle Callebaut,
- Jean-Christophe Gelly,
- Isabelle Hatin,
- Olivier Namy,
- Maxime Renard,
- Olivier Lespinet,
- and Anne Lopes
Genome Res. December 2021 31: 2303-2315; Published in Advance November 22, 2021, doi:10.1101/gr.275638.121
...predicted as foldable. Then, we investigated the early stages of de novo gene birth by reconstructing the ancestral sequences of 70 yeast de novo genes and characterized the sequence and structural properties of intergenic ORFs with a strong translation signal. This enabled us to highlight sequence...
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Research: Androgen receptor–mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells
- Johannes Hiltunen,
- Laura Helminen,
- Niina Aaltonen,
- Kaisa-Mari Launonen,
- Hanna Laakso,
- Marjo Malinen,
- Einari A. Niskanen,
- Jorma J. Palvimo,
- and Ville Paakinaho
Genome Res. August 2025 35: 1717-1732; Published in Advance June 2, 2025, doi:10.1101/gr.280224.124
...Androgen receptor–mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells Johannes Hiltunen1,3, Laura Helminen1,3, Niina Aaltonen1,3, Kaisa-Mari Launonen1, Hanna Laakso1, Marjo Malinen2, Einari A. Niskanen1, Jorma J. Palvimo1 and Ville...
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