title: Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis.
abstract: Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to increased rates of cell proliferation and tumorigenicity. We also observe that regulation of replication-dependent histone H2A expression can occur on a gene-specific level. Specific replication-dependent histone H2A genes are either up- or downregulated in chronic lymphocytic leukemia tumor tissue samples. In addition, discreet elements are identified in the 5' untranslated region of the HIST1H2AC locus that confer translational repression. Taken together, these results indicate that replication-dependent histone isoforms can possess distinct cellular functions and that regulation of these isoforms may play a role in carcinogenesis.
authors: Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA, Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors: Rajbir
authors: R
authors: Singh
authors: Amir
authors: A
authors: Mortazavi
authors: Kelly H
authors: KH
authors: Telu
authors: Prabakaran
authors: P
authors: Nagarajan
authors: David M
authors: DM
authors: Lucas
authors: Jennifer M
authors: JM
authors: Thomas-Ahner
authors: Steven K
authors: SK
authors: Clinton
authors: John C
authors: JC
authors: Byrd
authors: Michael A
authors: MA
authors: Freitas
authors: Mark R
authors: MR
authors: Parthun
mesh_terms: D020121:5' Untranslated Regions; D063646:Carcinogenesis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry; D004261:DNA Replication; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D002843:Chromatin; D006657:Histones; D020033:Protein Isoforms
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