Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSS815G)

• DOT Name: Histone H1.1 (H1-1)
• Synonyms: Histone H1a
• Gene Name: H1-1
• Related Disease:
  Acute myelogenous leukaemia
  Prostate cancer
  Prostate carcinoma
• UniProt ID: H11_HUMAN
• Pfam ID: PF00538
• Sequence:
  MSETVPPAPAASAAPEKPLAGKKAKKPAKAAAASKKKPAGPSVSELIVQAASSSKERGGV
  SLAALKKALAAAGYDVEKNNSRIKLGIKSLVSKGTLVQTKGTGASGSFKLNKKASSVETK
  PGASKVATKTKATGASKKLKKATGASKKSVKTPKKAKKPAATRKSSKNPKKPKTVKPKKV
  AKSPAKAKAVKPKAAKARVTKPKTAKPKKAAPKKK
• Function: Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation.
• Reactome Pathway:
  Formation of Senescence-Associated Heterochromatin Foci (SAHF) (R-HSA-2559584)
  Apoptosis induced DNA fragmentation (R-HSA-140342)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Limited	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[2]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone H1.1 (H1-1).	[3]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Histone H1.1 (H1-1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H1.1 (H1-1).	[8]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Histone H1.1 (H1-1).	[9]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Histone H1.1 (H1-1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Histone H1.1 (H1-1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Histone H1.1 (H1-1).	[7]

References

• [1] Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation.Clin Epigenetics. 2019 Oct 12;11(1):141. doi: 10.1186/s13148-019-0738-6.
• [2] A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.PLoS Genet. 2014 Nov 20;10(11):e1004809. doi: 10.1371/journal.pgen.1004809. eCollection 2014 Nov.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [5] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [6] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.