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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
...corresponds with their phenotypic severity. The two variants affect similar sets of enhancers, and p.E168d2 has distinct effects on silencers. Cis-regulatory elements (CREs) near cone photoreceptor genes are enriched for silencers that are derepressed in the presence of p.E168d2. Chromatin environments of CRX...
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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
...variants (no benign variants are colocated).Furthermore, the LP + reporter cell line is a synthetic transcriptional environment, lacking many of the partner TFs typically expressed in photoreceptors. In the retina, CRX is known to cobind at cis-regulatory elements with a number of TFs, including NRL, OTX2...
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Research: Aberrant homeodomain–DNA cooperative dimerization underlies distinct developmental defects in two dominant CRX retinopathy models
- Yiqiao Zheng,
- Gary D. Stormo,
- and Shiming Chen
Genome Res. February 2025 35: 242-256; Published in Advance December 23, 2024, doi:10.1101/gr.279340.124
...remodeling at photoreceptor CREs enriched with K50 HD motifs. (A) Heatmaps depicting the normalized ATAC-seq or CRX ChIP-seq signal intensities at CrxK88N-reduced accessible ATAC-seq peaks. (B) PWM logo and enrichment significance E-value of the STREME de novo discovered HD motif. (C) Line plot showing...
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Method: Massively parallel cis-regulatory analysis in the mammalian central nervous system
- Susan Q. Shen,
- Connie A. Myers,
- Andrew E.O. Hughes,
- Leah C. Byrne,
- John G. Flannery,
- and Joseph C. Corbo
Genome Res. February 2016 26: 238-255; Published in Advance November 17, 2015, doi:10.1101/gr.193789.115
...-seq enhancer study (White et al. 2013) in which short (84 bp) CREs (synthesized by oligonucleotide array) were assayed upstream of a rod photoreceptor-specific proximal promoter. These short CREs corresponded to retinal CRX ChIP-seq peaks, which are essentially a subset of retinal DHSs (Wilken et al. 2015...
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Resource: A temporal in vivo catalog of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements
- Salam Idriss,
- Mohammad Hallal,
- Abdullah El-Kurdi,
- Hasan Zalzali,
- Inaam El-Rassi,
- Erik A. Ehli,
- Christel M. Davis,
- Philip E.D. Chung,
- Deena M.A. Gendoo,
- Eldad Zacksenhaus,
- Raya Saab,
- and Pierre Khoueiry
Genome Res. February 2023 33: 269-282; Published in Advance January 17, 2023, doi:10.1101/gr.277037.122
..., respectively (Fig. 6G) (Supplemental Tables S15, S16). To identify PB-specific SEs, we intersected SEs with a set of 281,310 defined ENCODE CREs (Supplemental Methods) and identified 37 intergenic SEs at P90 (Fig. 6G, red dots), targeting genes with known role in the biology of the pineal gland like Crx...
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Research: A massively parallel reporter assay reveals context-dependent activity of homeodomain binding sites in vivo
- Andrew E.O. Hughes,
- Connie A. Myers,
- and Joseph C. Corbo
Genome Res. October 2018 28: 1520-1531; Published in Advance August 29, 2018, doi:10.1101/gr.231886.117
...CRX, prefer cytosines 3′ of each TAAT half-site (5′-TAATCNGATTA-3′). In an earlier study, we mapped CRX occupancy in mouse photoreceptors by ChIP-seq, which showed that CRX-bound regions in vivo are enriched for both monomeric and dimeric CRX binding sites (Corbo et al. 2010). However, whether...
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Method: Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches
- Muyoung Lee,
- Qingqing Guo,
- Mijeong Kim,
- Joonhyuk Choi,
- Alia Segura,
- Alper Genceroglu,
- Lucy LeBlanc,
- Nereida Ramirez,
- Yu Jin Jang,
- Yeejin Jang,
- Bum-Kyu Lee,
- Edward M. Marcotte,
- and Jonghwan Kim
Genome Res. March 2024 34: 484-497; Published in Advance April 5, 2024, doi:10.1101/gr.277926.123
...cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act...
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Resource: PRISM offers a comprehensive genomic approach to transcription factor function prediction
- Aaron M. Wenger,
- Shoa L. Clarke,
- Harendra Guturu,
- Jenny Chen,
- Bruce T. Schaar,
- Cory Y. McLean,
- and Gill Bejerano
Genome Res. May 2013 23: 889-904; Published in Advance February 4, 2013, doi:10.1101/gr.139071.112
...for four transcription factors with literature-confirmed PRISM biological function predictions. For all four factors, a single ChIP-seq experiment in a single context confirms a considerable fraction of the predicted sites: from 7% for CRX (mouse) to 56% for REST (human). Importantly, this represents...
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