Table 3.
Histone variants’ tissues expression location, histone chaperones and remodelers and clinical/pathological importance as biomarker/prognostic indicator. This table summarized all the 19 H2A variant’s’ tissues expression location, their corresponding histone chaperones, or remodelers responsible for deposition or exchange in or out the chromatin, and their clinicopathological importance as a prognostic indicator or biomarker for different types of cancers at vary expression levels.
| Variants’ Name | Location of Tissues | Chaperone and Remodeler | Clinicopathological Importance/Prognostic Value/Biomarker in Cancer Types |
|---|---|---|---|
| H2A.X | All tissues | FACT | High γ-H2A.X: 1. Biomarker for defect in DDR 2. Identified in cervical cancer, CRC, melanoma and OC 3. Access chemotherapy or radiotherapy effectiveness 4. Evaluate patient’s response to chemo-drug treatment and radiosensitivity 5. Predict high risk or early detection of cancers |
| H2A.Z | All tissues (pericentric heterochromatin in undifferentiated cells, TSS, centromere and enhancer regions) | ANP32E SRCAP INO80 |
High H2A.Z level: 1. Identified in breast cancer, CRC, liver, lung, prostate, bladder cancer, PDAC and metastatic melanoma 2. Poorer survival prediction 3. Therapeutic target for chemotherapy (cisplatin) 4. As biomarker for early PDAC and CRC detection |
| H2A.Z.1 | All tissues (regulatory regions and heterochromatin) | ANP32E SRCAP INO80 P400 |
High H2A.Z.1 level: 1. Identified in breast tumor, PDAC and HCC 2. Indicator for lymph node metastasis and poorer survival prediction 3. Indicator for predicting which treatments patients respond the best |
| H2A.Z.2 | All tissues (regulatory regions and heterochromatin) | P400 SRCAP |
High H2A.Z.2 level: 1. Identified in PDAC 2. Not known for any prognostic and biomarker value |
| H2A.Z.2.2 | All tissues (but predominantly in human brain) | TIP60 P400 SRCAP |
High H2A.Z.2.2 level: 1. Identified in PDAC only 2. Not known for any prognostic and biomarker value |
| MacroH2A1 | All tissues (Constitutive and facultative heterochromatin) | E3 ligase Cullin3SPOP | High macroH2A1 level: 1. Indicator of worst prognosis in different breast cancer types 2. Diagnostic indicator for HCC and lung cancer recurrence 3. Indicator for poor outcome prediction in HCC |
| MacroH2A2 | All tissues (Constitutive and facultative heterochromatin) | Unknown | High macroH2A2 level: 1. Indicator of worst prognosis in different breast cancer types 2. Indicator of recurrence free survival in anal neoplasm Low macroH2A2 level: 1. Indicator of high-grade and faster recurrence of anal neoplasm |
| MacroH2A1.1 | All tissues (Constitutive and facultative heterochromatin) | Unknown | High macroH2A1.1 level: 1. Biomarker for TNBC 2. Indicator of poorer survival prediction of TNBC 3. Biomarker for senescent cells in tumor Low macroH2A1.1 level: 1. Diagnostic indicator for lung cancer recurrence |
| MacroH2A1.2 | All tissues (Constitutive and facultative heterochromatin) | ATRX | High macroH2A1.2 level: 1. Biomarker for HER2 positive breast cancer |
| H2A.R | Testis-specific | Unknown | Unknown |
| H2A.Bbd | All tissues (euchromatin and testis) | NAP1 | High H2A.Bbd level: 1. Biomarker for HL, BLCA, UCEC, DLBCLs, etc. (required further research) |
| H2A.P | Originated on portion of X chromosome, testis-specific | Unknown | Unknown |
| H2A.Q | In testis of dogs and pigs only | Unknown | Unknown |
| H2A.L | Lost in human, conserved in mouse, testis-specific | Unknown | Unknown |
| H2A.L.2 | Lost in human, testis-specific | Unknown | Unknown |
| H2A.L.3 | Lost in human, testis-specific | Unknown | Unknown |
| H2A.22 (H2A.J) | In senescent cells’ chromatin, aging mice in tissue-specific manner and human skin | Unknown | High H2A.J level: 1. Poor prognostic marker in glioblastoma, KIRC, brain cancer and aggressive melanoma 2. Indicator for increasing survival rate in bladder, prostate and all subtypes of breast cancer 3. Biomarkers for senescent stem and aging skin cells 4. Indicator for cancer that exhibit chemotherapy resistance |
| H2A.1 | X chromosome, autosomes, testis, oocytes and zygote | NPM2 | High H2A.1 level: 1. Biomarker for HCC and colon cancer detection (required further research) |
| H2A.2 | Unknown | Unknown | High H2A.2 level: 1. Biomarker for colon cancer detection (required further research) |
Abbreviations: DDR: DNA damage repair; CRC: colorectal cancer; OC: ovarian cancer; HCC: hepatocellular carcinoma; FACT: Facilitate Chromatin Transcription; ANP32E: Acidic Nuclear Phosphoprotein 32 Family Member E; ANP32B: Acidic Nuclear Phosphoprotein 32B; INO80: human Inositol auxotrophy 80; SRCAP: Snf2 Related CREBBP Activator Protein; NAP1: Nucleosome Assembly Protein 1; TSS: transcription start site; PDAC: pancreatic ductal adenocarcinoma; TNBC: Triple Negative Breast Cancer; HER2: Human Epidermal Growth Factor Receptor 2; HL: Hodgkin’s lymphoma; BLCA: urothelial bladder carcinomas; UCEC: Uterine Corpus Endometrial Carcinomas; DLBCLs: Diffuse Large B-cell Lymphomas; KIRC: Kidney Renal Cell Carcinoma.