title: Genome-wide distribution of histone H4 Lysine 16 acetylation sites and their relationship to gene expression.
abstract: BACKGROUND
  Histone post-translational modifications are critical determinants of chromatin structure and function, impacting multiple biological processes including DNA transcription, replication, and repair. The post-translational acetylation of histone H4 at lysine 16 (H4K16ac) was initially identified in association with dosage compensation of the Drosophila male X chromosome. However, in mammalian cells, H4K16ac is not associated with dosage compensation and the genomic distribution of H4K16ac is not precisely known. Therefore, we have mapped the genome-wide H4K16ac distribution in human cells.
  
  
  RESULTS
  We performed H4K16ac chromatin immunoprecipitation from human embryonic kidney 293 (HEK293) cells followed by hybridization to whole-genome tiling arrays and identified 25,893 DNA regions (false discovery rate <0.005) with average length of 692 nucleotides. Interestingly, although a majority of H4K16ac sites localized within genes, only a relatively small fraction (~10%) was found near promoters, in contrast to the distribution of the acetyltransferase, MOF, responsible for acetylation at K16 of H4. Using differential gene expression profiling data, 73 genes (> ±1.5-fold) were identified as potential H4K16ac-regulated genes. Seventeen transcription factor-binding sites were significantly associated with H4K16ac occupancy (p < 0.0005). In addition, a consensus 12-nucleotide guanine-rich sequence motif was identified in more than 55% of the H4K16ac peaks.
  
  
  CONCLUSIONS
  The results suggest that H4K16 acetylation has a limited effect on transcription regulation in HEK293 cells, whereas H4K16ac has been demonstrated to have critical roles in regulating transcription in mouse embryonic stem cells. Thus, H4K16ac-dependent transcription regulation is likely a cell type specific process.
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: G.N.R. Center for Genome Informatics Unit, CSIR- Institute of Genomics and Integrative Biology, Delhi, 110007, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA.
authors.forename: Girdhar G
authors.initials: GG
authors.lastname: Sharma
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA.
authors.forename: Clayton R
authors.initials: CR
authors.lastname: Hunt
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Westover
authors.affiliation: G.N.R. Center for Genome Informatics Unit, CSIR- Institute of Genomics and Integrative Biology, Delhi, 110007, India.|G.N.R. Center for Genome Informatics and Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA.
authors.forename: Tej K
authors.initials: TK
authors.lastname: Pandita