Journal: Current Biology

Article Title: Myelination of Neuronal Cell Bodies when Myelin Supply Exceeds Axonal Demand

doi: 10.1016/j.cub.2018.02.068

Figure Lengend Snippet: Increasing Oligodendrocyte Number Recapitulates Wrapping of Neuronal Cell Bodies (A) Double myelin and oligodendrocyte reporter (4 dpf), treated with vehicle DMSO, Skp2C25, or GANT61. (B and C) Oligodendrocyte (e.g., asterisk) number and myelinated cell bodies (e.g., arrowheads) number is increased in the dorsal spinal cord of Skp2C25-treated animals and reduced in GANT61-treated animals, quantified in (B) (p [Skp2C25-DMSO] = 0.0004, n = 20 DMSO and n = 10 Skp2C25; p [C646-DMSO] < 0.0001, n = 22 DMSO and n = 19 C646; p [GANT61-DMSO] < 0.0001, n = 9 DMSO and n = 13 GANT61; t tests; data normalized to control average) and in (C) (p [Skp2C25-DMSO] < 0.0001, n = 20 DMSO and n = 10 Skp2C25; p [C646-DMSO] < 0.0001, n = 22 DMSO and n = 19 C646; p [GANT61-DMSO] = 0.011, n = 9 DMSO and n = 13 GANT61; t tests; data normalized to control average; GANT61 data and its control plotted on right y axis), respectively. (D) Plotting all normalized data shows that myelinated cell body number positively correlates to oligodendrocyte number (Pearson’s r correlation and p value displayed for each treatment). (E) TEM of 4 dpf medial-dorsal spinal cord shows increased number of myelinated axons (red asterisks) in Skp2C25-treated animals whereas controls still have many unmyelinated large-caliber axons (green circles). (F) Total number of large-caliber (>0.5 μm diameter) axons in the medial-dorsal spinal cord is normal in Skp2C25-treated animals (p = 0.852; n = 4 DMSO and n = 5 Skp2C25; t test). (G) Myelinated axon number is increased with Skp2C25 (p = 0.006; n = 8 DMSO and n = 9 Skp2C25; t test). (H) Smallest myelinated axons in Skp2C25-treated animals remain above 0.4 μm diameter (p = 0.961 for all bin comparisons; n = 7 DMSO and n = 9 Skp2C25; corrected t tests). (I) 4 dpf double myelin and Rohon-Beard (RB) neuron reporter (Tg(isl1(ss):Gal4; UAS:DsRed)), focusing in the dorsal spinal cord. (J and K) Skp2C25-treated animals have more “very dorsal” myelin sheaths (arrows), quantified in (J) (p = 0.011; n = 19 DMSO and n = 19 Skp2C25; t test), which add up to a higher total myelin sheath length, quantified in (K) (p = 0.013; n = 19 DMSO and n = 19 Skp2C25; t test), as well as readily identifiable myelinated cell bodies (arrowheads). Examples of very rare myelin sheaths on dsRed+ large-caliber RB axons (arrows in merged panels), which are not increased with Skp2C25 (see main text for details), are shown. All graphs display mean and SD. The scale bars represent 20 μm (A) and 10 μm (I). See also Figure S1 .

Article Snippet: C646, p300/CBP inhibitor , Xcess Biosciences , Cat#: M60129-2 s, CAS: 328968-36-1.

Techniques: Control

Journal: Current Biology

Article Title: Myelination of Neuronal Cell Bodies when Myelin Supply Exceeds Axonal Demand

doi: 10.1016/j.cub.2018.02.068

Figure Lengend Snippet:

Article Snippet: C646, p300/CBP inhibitor , Xcess Biosciences , Cat#: M60129-2 s, CAS: 328968-36-1.

Techniques: Recombinant, Software

Journal: Development (Cambridge, England)

Article Title: High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

doi: 10.1242/dev.139220

Figure Lengend Snippet: Biological process and network analysis of vegetally enriched transcripts. (A) The 198 annotated transcripts upregulated in the vegetal pole categorized according to their biological function (GeneCards). (B) Sixty vegetally enriched transcripts with enzymatic activity grouped based on enzymatic function. (C) GeneGo pathway analysis using the direct interaction algorithm of vegetally enriched transcripts. (D) RT-qPCR verification of pathway hubs p300, irf8 and err1/esrra at animal (An) versus vegetal (Vg) poles. vg1, control for vegetal pole.

Article Snippet: Inhibition of p300 significantly reduced PGC number in a dose-dependent manner, suggesting a role in PGC development ( ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 8. caption a7 Inhibition of p300 reduces PGC number. (A) Schematic of GeneGo-predicted p300 regulatory interconnections from our data set. (B-G) One-cell embryos were incubated with ≤0.04% DMSO (ctrl, n =31) or increasing concentrations of the p300 inhibitor C646: 0.2 μM, n =38; 0.5 μM, n =34; 1 μM, n =34; 2 μM, n =34.

Techniques: Activity Assay, Quantitative RT-PCR, Control

Journal: Development (Cambridge, England)

Article Title: High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

doi: 10.1242/dev.139220

Figure Lengend Snippet: Inhibition of p300 reduces PGC number. (A) Schematic of GeneGo-predicted p300 regulatory interconnections from our data set. (B-G) One-cell embryos were incubated with ≤0.04% DMSO (ctrl, n=31) or increasing concentrations of the p300 inhibitor C646: 0.2 μM, n=38; 0.5 μM, n=34; 1 μM, n=34; 2 μM, n=34. Tailbud embryos were analyzed for xpat expression by WISH. The average number of PGCs per embryo was quantified (B). *P<0.05 compared with uninjected control.

Article Snippet: Inhibition of p300 significantly reduced PGC number in a dose-dependent manner, suggesting a role in PGC development ( ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 8. caption a7 Inhibition of p300 reduces PGC number. (A) Schematic of GeneGo-predicted p300 regulatory interconnections from our data set. (B-G) One-cell embryos were incubated with ≤0.04% DMSO (ctrl, n =31) or increasing concentrations of the p300 inhibitor C646: 0.2 μM, n =38; 0.5 μM, n =34; 1 μM, n =34; 2 μM, n =34.

Techniques: Inhibition, Incubation, Expressing, Control

Journal: bioRxiv

Article Title: CpG island density predicts CBP/p300 dependency across 3D chromatin clusters

doi: 10.64898/2026.05.04.722036

Figure Lengend Snippet: a. Overview of Pol2 HiChIP derived clusters. b. Clusters ranked by the percentage of their loop anchors overlapping CpG islands, broken into high, medium and low CpG content. c. Overlap of cluster features, including promoter-promoter loops, p300 and PAX3-FOXO1 ChIP-seq peak overlap, and target gene categories (Core Regulatory Transcription Factors and Housekeeping gene), at clusters ranked by percent CpG islands at anchors. d. Percentage of CpG islands at loop anchors within clusters, separated by gene category. e. Total Pol2 contacts per million (CPM) signal among clusters grouped by CpG content. f. Gene expression from RNA-seq (log2 transcripts per million, TPM) among clusters grouped by CpG content. g. Percentage of promoter-promoter loops among clusters grouped by CpG content. h. Frequency of PAX3-FOXO1 binding at loop anchors in clusters grouped by CpG content. i. Frequency of p300 binding at loop anchors in clusters grouped by CpG content. j. Gene expression changes in RMS cells after dual CRISPR mediated knockout of CBP and EP300, for genes in clusters grouped by CpG content. k. GAPDH and MYOD1 gene regulatory clusters, shown with Pol2 HiChIP clustering, CpG island abundance, P3F and p300 binding, H3K27ac and Pol2 ChIP-seq levels, and RNA-seq, revealing distinct cluster features. l. Model of CpG rich Housekeeping clusters vs. p300 rich Core Regulatory clusters.

Article Snippet: In 2022, a team at GlaxoSmithKline identified proline-based p300 inhibitors from a DNA-encoded library.

Techniques: HiChIP, Derivative Assay, ChIP-sequencing, Gene Expression, RNA Sequencing, Binding Assay, CRISPR, Knock-Out

Journal: bioRxiv

Article Title: CpG island density predicts CBP/p300 dependency across 3D chromatin clusters

doi: 10.64898/2026.05.04.722036

Figure Lengend Snippet: a. Molecular structure of IHK-44. b. IHK-44 docked to the HAT domain of p300. c-d. Dose-response ( c ) and time-course ( d ) Western blot of RH4 cells after IHK-44 treatment. Dose-response samples were treated for 6 h each. Time-course samples were treated at 100 nM each. H2B and H3 are shown as loading controls. e. Heatmaps of HBK16ac and H2BK20ac ChIP-seq shows that p300-bound enhancers are downregulated after 100 nM IHK-44 treatment over a 6 h time-course treatment period.

Article Snippet: In 2022, a team at GlaxoSmithKline identified proline-based p300 inhibitors from a DNA-encoded library.

Techniques: Western Blot, ChIP-sequencing

Journal: bioRxiv

Article Title: CpG island density predicts CBP/p300 dependency across 3D chromatin clusters

doi: 10.64898/2026.05.04.722036

Figure Lengend Snippet: a. Schematic of CHESS-DIA methodology. b. Violin plots of normalized protein abundance levels of CBP (left) and p300 (right) across nuclear compartments. c. Box plots of protein abundance levels between CBP (top) and p300 (bottom) in euchromatin fractions from RH4 cells treated with DMSO or increasing concentrations of IHK-44 (100 nM, 125 nM, 150 nM). Box plots represent median and quartiles, whiskers representing 1.5 x IQR. Statistical significance determined using a two-tailed Welch’s T-test. d. Box plots of protein abundance levels between PAX3-FOXO1, MYOD1, AND MYOG in euchromatin fractions from RH4 cells treated with DMSO or increasing concentrations of IHK-44 (100 nM, 125 nM, 150 nM). Box plots represent median and quartiles, whiskers representing 1.5 x IQR. Statistical significance determined using a two-tailed Welch’s T-test. e. Scatter plot comparing changes between RNA and protein abundance in RH4 cells treated with DMSO or 100 nM IHK-44 for 6 h. Lineage-specific TFs are highlighted and labeled in red, housekeeping genes in blue, other genes in gray.

Article Snippet: In 2022, a team at GlaxoSmithKline identified proline-based p300 inhibitors from a DNA-encoded library.

Techniques: Quantitative Proteomics, Two Tailed Test, Labeling

Journal: bioRxiv

Article Title: CpG island density predicts CBP/p300 dependency across 3D chromatin clusters

doi: 10.64898/2026.05.04.722036

Figure Lengend Snippet: a. Dose-response curves showing relative cell viability of FP-RMS (RH4), FN-RMS (RD), and normal myoblast (KM155C25DIST) cells after 72 h treatment with IHK-44. Values represent mean ± SEM of n = 4 technical replicates. b. Growth curves of % confluence over time (h) in FP-RMS (RH4, RH5), FN-RMS (CTR), and normal myoblast (HSMM) cell lines treated with DMSO or 185 nM IHK-44. Values represent mean ± SEM of n = 3 technical replicates. c. Heatmap summarizing IC 50 values (nM) for CBP/p300 bromodomain inhibitors (CCS1477, GNE-049), CBP/p300 HAT domain inhibitors (A-485, IHK-44), p300 degrader (JQAD1), and CBP/p300 degraders (dCBP-1, CBPD-409) across sensitive and resistant RMS cell lines. d. Bar plots summarizing cell-cycle arrest of RH4 cells treated with increasing doses (10, 100, 1000 nM) of IHK-44 for 72 h. e. Bar plots summarizing apoptosis Annexin V/PI staining of RH4 cells treated with increasing doses (10, 100, 1000 nM) of IHK-44 for 72 h. f. IC 50 values across 958 cell lines treated with IHK-44 from the PRISM screen grouped by primary disease. Box plot represents median and quartiles, whiskers showing 1.5 × IQR. Fusion-positive RMS is highlighted and labeled in red. Fusion-negative RMS in highlighted and labeled in red. g. Correlation between IHK-44 efficacy (log2.AUC) and other compounds in the DepMap Repurposing dataset. A-485 is highlighted and labeled in red. h. Correlation between IHK-44 efficacy (log2.AUC) and gene dependency scores in the DepMap CHRONOS dataset. p300 is highlighted and labeled in red. i. Western blots of non-treated histone acetylation levels in a panel of sensitive and resistant RMS cell lines. H2B and H3 are shown as loading controls

Article Snippet: In 2022, a team at GlaxoSmithKline identified proline-based p300 inhibitors from a DNA-encoded library.

Techniques: Staining, Labeling, Western Blot

Journal: bioRxiv

Article Title: CpG island density predicts CBP/p300 dependency across 3D chromatin clusters

doi: 10.64898/2026.05.04.722036

Figure Lengend Snippet: a. Design of a Random Forest machine learning model for predicting response to CBP/p300 inhibition at 6 hours, considering a mix of gene features, followed by SHAP permutation to learn the relative importance of each feature to predict responsiveness. b. The ROC (true positive versus false positive) curves for classification models from each gene feature group, and the combination of all features. Each line is colored according to the feature colors in ( a. ). AUC, area under the curve. c. The precision-recall curves for classification models from each gene feature group, and the combined all feature performance. Each line is colored according to the feature colors in ( a. ). AP, Average Precision. d. SHAP feature importance analysis colored by feature group across 100 regression runs. Each boxplot is colored according to the feature group colors in ( a. ).

Article Snippet: In 2022, a team at GlaxoSmithKline identified proline-based p300 inhibitors from a DNA-encoded library.

Techniques: Inhibition