Histone H4 Phosphorylation: Affecting Liver Regeneration and Cancer

Fri, 11/01/2013 - 09:17

Histones are highly conserved proteins that function in the organization of nuclear DNA to create chromatin in eukaryotic cells. Post-translational alterations of histones are critical to monitoring and regulating DNA structure, expression, and gene transcription. There are five histones: H1, H2A, H2B, H3, and H4. Histone H4 consists of 102 amino acid residues and frequently acts as a docking site for other histones. Histone H4’s N-terminal tail undergoes acetylation, methylation, and phosphorylation: all vital for regulation of gene transcription. The degree of modification is controlled by kinases and phosphates because the majority of histone phosphorylation sites lie on the histone’s N-terminal tails. Structurally, histones H2A and H2B bond to generate dimers while histones H3 and H4 combine to produce tetrameters. The combination of the H2A/H2B dimers and the H3/H4 tetramers create the nucleosome core.  The nucleosome core is a repeating structural unit of chromatin that is critical for the first order of DNA packing. It gives the chromatin the characteristic “beads-on-a-string” appearance and without it, DNA would not be able to be compacted.

Immunocytochemistry/Immunofluorescence: Histone H4 [Monomethyl Arg3] Antibody Immunocytochemistry/Immunofluorescence: Histone H4 [Monomethyl Arg3] Antibody

Research is beginning to investigate the consequences of phosphorylation of histone H4. In the liver, phosphorylation of histone H4 occurs in liver cells on at least one of the two histidine residues. Phosphorylation by histone H4 histidine kinase activity coincides with proliferation and differentiation of liver progenitor cells. This process is associated with production of hepatocytes—the chief operational cell of the liver that functions to regulate metabolic, endocrine, and secretory functions. Consequently, histone H4 histidine activity also appears to account for approximately 80% of liver cell regeneration following chemical or mechanical damage (1). Conversely, researchers have found that certain expression patterns of histone H4 are linked to negative psychological conditions including the development and progression of certain cancers, implicating that histone H4 as an oncoprotein. Thus, current research is now geared toward investigating its possible role as a diagnostic marker for hepatocellular carcinoma as well as for classifying various preneoplastic lesions (2).

  1. PMID: 22260708
  2. PMID: 15240507

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Written by Kelsey Repine

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