|Camporeale, Gabriela - UNI OF NE-LINCOLN|
|Oommen, Anna - UNI OF NE - LINCOLN|
|Griffin, Jacob - UNI OF NE - LINCOLN|
|Zempleni, Janos - UNI OF NE-LINCOLN|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 6, 2006
Publication Date: November 1, 2007
Citation: Camporeale, G., Oommen, A.M., Griffin, J.B., Sarath, G., Zempleni, J. 2007. K12-bioitinylated histone H4 marks heterochromatin in human lymphoblastoma cells. Journal of Nutritional Biochemistry. 18:760-768. Interpretive Summary: Histones are DNA binding proteins and an integral part of chromatin structure. Covalent modification of histones at amino acid residues by small molecules such as biotin, phosphate etc marks the DNA for defined outcomes such as transcription, silencing or repair. Thus, specific marks on histones can be used to decipher important changes in cell status. In this study we used antibodies generated to a specific histone mark (biotinylated lysine12 on histone H4) to define a role for this histone modification. Our results indicate that biotinylation of lysine12 on H4 is associated predominantly with regions of the DNA that are silent (heterochromatin; low transcriptional activity). Our data are consistent with a novel role for biotin in chromatin structure and transcriptional activity of genes.
Technical Abstract: Covalent modifications of histones play crucial roles in chromatin structure and genomic stability. Recently, we reported a novel modification of histones: biotinylation of lysine residues. Here we provide evidence that K12-biotinylated histone H4 (K12Bio H4) maps specifically to both constitutive heterochromatin (alpha satellite repeats in pericentromeric regions) and facultative heterochromatin ('-G globin and interleukin-2) in human lymphoblastoma cells. The abundance of K12Bio H4 in these regions was similar to that of K9-dimethylated histone H3, a known marker for heterochromatin. Likewise, K8-biotinylated histone H4 (K8Bio H4) mapped to heterochromatin, but the relative enrichment was smaller compared with K12Bio H4. Stimulation of interleukin-2 transcriptional activity with phorbol-12-myristate-13-acetate and phytohemagglutinin caused a rapid depletion of K12Bio H4 in the gene promoter. These data are consistent with a novel role for biotin in chromatin structure and transcriptional activity of genes.