Translating the histone code into leukemia.
The "histone code" is comprised of the covalent modifications of histone tails that function to regulate gene transcription. The post-translational modifications that occur in histones within the regulatory regions of genes include acetylation, methylation, phosphorylation, ubiquitination, sumoylation, and ADP-ribosylation. These modifications serve to alter chromatin structure and accessibility, and to act as docking sites for transcription factors or other histone modifying enzymes. Several of the factors that are disrupted by chromosomal translocations associated with hematological malignancies can alter the histone code in a gene-specific manner. Here, we discuss how the histone code may be disrupted by chromosomal translocations, either directly by altering the activity of histone modifying enzymes, or indirectly by recruitment of this type of enzyme by oncogenic transcription factors. These alterations in the histone code may alter gene expression pattern to set the stage for leukemogenesis.
Linggi
Bryan E
BE
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Brandt
Stephen J
SJ
Sun
Zu-Wen
ZW
Hiebert
Scott W
SW
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000737:chemistry; D002875:Chromosomes / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051560:Proto-Oncogene Proteins c-bcl-6; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D002843:Chromatin; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D006657:Histones; D051560:Proto-Oncogene Proteins c-bcl-6; D011993:Recombinant Fusion Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases