Journal: bioRxiv

Article Title: Workload-induced changes to cell state contribute to β-cell failure in diabetes

doi: 10.64898/2026.05.13.725004

Figure Lengend Snippet: (a) Schematic of alleles and treatments used to inactivate Lsd1 in db/db mice. TM, tamoxifen; wks, weeks. (b) Time course of ad libitum-fed blood glucose levels in TM-treated mice of the indicated genotypes. db/+ Lsd1 fl/+β : n = 7 mice, db/db Lsd1 fl/+β : n = 8 mice, db/db Lsd1 Δβ : n = 11 mice, db/+ Lsd1 Δβ : n = 14 mice. * p <0.05, ** p <0.01, *** p <0.001 between db/db Lsd1 fl/+β and db/db Lsd1 Δβ mice. (c) Glucose tolerance tests in TM-treated mice of the indicated genotypes. db/+ Lsd1 fl/+β : n = 6 mice, db/db Lsd1 Δβ : n = 11 mice, db/db Lsd1 fl/+β : n = 13 mice. * p <0.05, ** p <0.01 between db/db Lsd1 fl/+β and db/db Lsd1 Δβ mice. (d) Serum insulin and blood glucose (glc) levels in mice of the indicated genotypes following a 6-hour fast or 10 min following intraperitoneal injection of glucose. db/+ Lsd1 fl/+β fast and 10’ glucose: n = 4 mice, db/db Lsd1 Δβ 10’ glucose: n = 5 mice, all other groups: n = 6 mice. (e and f) Static insulin secretion assays for islets from the indicated genotypes of mice stimulated with the indicated glucose (glc) concentrations (in mM) with or without 10 nM of exendin-4 (Ex4) or GIP at 7 wks (e) and 9 wks (f) of age. db/+ Lsd1 fl/+β 16.8 mM glc + Ex4 or GIP wk 7: n = 4 pools of 10 islets each, db/+ Lsd1 Δβ 16.8 mM glc + Ex4 or GIP wk 7 and db/db Lsd1 fl/+β 16.8 mM glc + Ex4 wk 7: n = 5 islet pools, db/+ Lsd1 fl/+β 16.8 mM glc wk 7: n = 10 islet pools, db/+ Lsd1 fl/+β 2.8 mM glc wk 9 and db/db Lsd1 fl/+β 16.8 mM glc wk 9: n = 11 islet pools, db/db Lsd1 fl/+β 2.8 mM glc wk 9, db/db Lsd1 Δβ 2.8 mM glc or 16.8 mM glc wk 9, db/+ Lsd1 fl/+β 16.8 mM glc wk 9, and all genotypes 16.8 mM glc + Ex4 wk 9: n = 12 islet pools, all other groups: n = 6 islet pools. (g and h) Islet insulin content for islets from the indicated genotypes of mice. db/+ Lsd1 Δβ wk 7: n = 12 pools of 10 islets each, db/+ Lsd1 fl/+β wk 7: n = 17 islet pools, db/+ Lsd1 Δβ wk 9: n = 23 islet pools, all other groups: n = 24 islet pools. (i) Schematic of S961 administration via transplanted minipumps (20 nmol/week). Veh, vehicle. (j) Time course of ad libitum-fed blood glucose levels in TM-treated Lsd1 fl/+ ; Pdx1-CreER mice ( Lsd1 fl/+ β ) and TM-treated Lsd1 fl/fl ; Pdx1-CreER mice ( Lsd1 Δβ ) administered S961 or vehicle. Lsd1 fl/+ β veh: n = 3, Lsd1 Δβ veh: n = 5, Lsd1 fl/+ β S961: n = 7, Lsd1 Δβ S961, n = 9. NS, not significant between S961-treated Lsd1 fl/+ β and Lsd1 Δβ mice. * p <0.05 between Lsd1 fl/+ β and Lsd1 Δβ mice (k and l) Blood glucose levels (k) and serum insulin levels (l) after a 6-hour fast in Lsd1 fl/+ β and Lsd1 Δβ treated with S961 or vehicle for the indicated weeks. Lsd1 fl/+ β veh: n = 3, Lsd1 Δβ veh: n = 5, Lsd1 fl/+ β S961: n = 7, Lsd1 Δβ S961, n = 9. Significance was determined by one-way ANOVA followed by Student’s t-test with Welch’s correction for unequal variance as necessary followed by Dunnett’s multiple comparisons test (g and h) or by two-way ANOVA for treatment or genotype interaction with time or stimulation condition followed by Sidak’s (b, c, j) or Benjamini, Krieger and Yekutieli multiple comparisons test (d - f, k, l). * p <0.05, ** p <0.01, *** p <0.001; NS, not significant.

Article Snippet: The following strains were used in this study: Lsd1 flox , Pdx1-creER , and db/db (Jackson labs strain 000642).

Techniques: Injection

Journal: Journal of Advanced Research

Article Title: Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma

doi: 10.1016/j.jare.2025.08.007

Figure Lengend Snippet: KAT2B destroyed HDAC5/LSD1 complex assembly and suppressed FASN transcriptional activity Co-IP assays were performed to verify the interaction strength between wild-type HDAC5 or the K726R mutant and Exportin1 with KAT2B overexpression. (B) Representative immunofluorescence images of wild-type HDAC5, K726R mutant HDAC5, and NES-deleted HDAC5 with KAT2B overexpression in RCC cells. (C-D) Western blots were used to assess HDAC5 and LSD1 expression in RCC cells with KAT2B overexpression or knockdown. (E) The interaction between HDAC5 and LSD1 was determined by Co-IP assays in RCC cells. (F) The interactions between HDAC5 (wild, K726Q, and K726R) and LSD1 were determined by Co-IP assays in 293 T cells. (G) RCC cells were treated with Eltanexor (60 nM) to inhibit Exportin1 activity. The levels of nuclear HDAC5, total HDAC5, Exportin1, and LSD1 were detected using Western blot. (H) Protein stability experiment of LSD1 in RCC cells with KAT2B overexpression after treated with 100 μM cycloheximide (CHX) for 0 h, 1 h, 2 h, 3 h, and 4 h and statistical diagram. (I) Following the addition of chloroquine (10 μM) or MG132 (8 μM) to RCC, LSD1 protein expression was assessed. (J) RCC cells with KAT2B overexpression were immunoprecipitated with LSD1 antibody, and the level of ubiquitin was detected. (K) LSD1 and FASN expression were detected in RCC cells with KAT2B (wild or dead) and/or HDAC5 (wild, 726Q or 726R) overexpression. (L) Schematic diagram illustrating KAT2B-mediated acetylation of HDAC5, promoting its cytoplasmic mislocalization, which resulted in the disruption of the HDAC5-LSD1 complex in the nucleus and subsequent LSD1 degradation.

Article Snippet: KAT2B overexpression and HDAC5 overexpression lentivirus, KAT2B‐targeted shRNA lentivirus, and overexpression plasmids of LSD1 and KAT2B (wild and enzyme-inactivated) was provided by Genechem Co. Ltd (China).

Techniques: Activity Assay, Co-Immunoprecipitation Assay, Mutagenesis, Over Expression, Immunofluorescence, Western Blot, Expressing, Knockdown, Immunoprecipitation, Ubiquitin Proteomics, Disruption

Journal: Journal of Advanced Research

Article Title: Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma

doi: 10.1016/j.jare.2025.08.007

Figure Lengend Snippet: The KAT2B/HDAC5/LSD1/FASN axis repressed RCC lipogenesis and progression in vivo B) The picture of xenografts using Caki-1 cells with KAT2B and/or HDAC5 stable overexpressing. The tumor weight was used for statistical comparison (n = 5). (C) The tumor volume of each group was measured every six days (n = 5). (D) Representative of immunohistochemical (IHC) staining for KAT2B, HDAC5, LSD1, FASN and Ki67 in tumor xenografts. (E) Oil red O staining of the tumor xenografts with KAT2B and/or HDAC5 overexpression. (F) Living fluorescence images of mice in the metastasis model. (G-H) The liver photo and H&E staining of liver tissue in the metastatic model. Data were analyzed by one-way ANOVA (B,C).

Article Snippet: KAT2B overexpression and HDAC5 overexpression lentivirus, KAT2B‐targeted shRNA lentivirus, and overexpression plasmids of LSD1 and KAT2B (wild and enzyme-inactivated) was provided by Genechem Co. Ltd (China).

Techniques: In Vivo, Comparison, Immunohistochemical staining, Immunohistochemistry, Staining, Over Expression, Fluorescence

Journal: Journal of Advanced Research

Article Title: Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma

doi: 10.1016/j.jare.2025.08.007

Figure Lengend Snippet: Graphic abstract of this research TET1-mediated promoter hypermethylation in RCC leaded to decreased KAT2B expression. Mechanistically, KAT2B acetylated HDAC5 at the K726 site and promoted its nucleus export, thereby failing to form a complex with LSD1 in nucleus. This leaded to increased histone methylation levels and decreased FASN expression, ultimately inhibiting lipogenesis and RCC progression. FASN inhibition might be useful in treating KAT2B-low RCC progression by targeting de novo lipogenesis.

Article Snippet: KAT2B overexpression and HDAC5 overexpression lentivirus, KAT2B‐targeted shRNA lentivirus, and overexpression plasmids of LSD1 and KAT2B (wild and enzyme-inactivated) was provided by Genechem Co. Ltd (China).

Techniques: Expressing, Methylation, Inhibition

Journal: bioRxiv

Article Title: Cancer-associated KBTBD4 mutations induce differentiation defects and confer a unique therapeutic vulnerability

doi: 10.64898/2026.03.12.711277

Figure Lengend Snippet: (A) Volcano plot showing global protein expression in HL60 cells transduced with P311PP mutant. Blue and red dots show significantly decreased or increased proteins (adjusted p-value<0.05). CoREST components RREB1, RCOR1, KDM1A, RCOR3, and ZNF217 are highlighted in the volcano plot. The global proteome data was plotted after excluding PCDHGA11. (B) High throughput compound screening in HL60 cells stably expressing RCOR1-GFP treated with UM171 (200nM). Schematic of the screening rationale (top panel). The compounds were added at a final concentration of 1µM, and flow analysis was performed after 3 hours post treatment to measure the relative GFP expression (bottom panel). Red dots show the hits from the screen and the table on right-side shows the functional classification of the hits. (C) A dose-titration experiment showing the rescue of RCOR1-GFP by two class I specific HDAC inhibitors (mocetinostat and romidepsin) and three Pan HDAC inhibitors (belinostat, pracinostat and vorinostat). GFP mean fluorescence intensity of DMSO treatment was used as controls. Data from 3 replicates from 1 of 2 independent experiments with similar results are shown. (D) RCOR1 protein levels in P311PP expressing HL60 cells either treated with DMSO, belinostat (320nM) or mocetinostat (300nM) for 3 hours. (E) RCOR1 ELM2-GFP clones were expressed in HL60 cells and analyzed for the interaction with HDAC2 through immunoprecipitation. The degradation profiles of the corresponding alanine substitution clones to UM171 treatment are represented as a heat map. (F) Schematic representation of the mechanistic basis of HDAC inhibitors in preventing the CoREST degradation.

Article Snippet: The proteins were transferred to iBlot 2 PVDF membranes (#IB24001, Thermo Fisher Scientific) and probed with the following primary antibodies: RCOR1 (#14567), KDM1A (LSD1, #2184S), HDAC2 (#5113T, all from Cell Signaling Technology), GFP (#ab290, Abcam), and Actin (#612656, BD Biosciences).

Techniques: Expressing, Transduction, Mutagenesis, High Throughput Screening Assay, Stable Transfection, Concentration Assay, Functional Assay, Titration, Fluorescence, Clone Assay, Immunoprecipitation