Genome-wide distribution of histone H4 Lysine 16 acetylation sites and their relationship to gene expression

Nobuo Horikoshi, Pankaj Kumar, Girdhar G. Sharma, Min Chen, Clayton R. Hunt, Kenneth Westover, Shantanu Chowdhury, Tej K. Pandita

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Article number3
JournalGenome Integrity
Volume4
Issue number1
DOIs
StatePublished - Apr 12 2013

Fingerprint

Acetylation
Histones
Lysine
Genome
Gene Expression
Kidney
Biological Phenomena
Guanine Nucleotides
Chromatin Immunoprecipitation
X Chromosome
Post Translational Protein Processing
DNA Replication
DNA Repair
Drosophila
Chromatin
Transcription Factors
Binding Sites
DNA
Genes

Keywords

  • Gene expression
  • Genome
  • H4K16ac

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Genome-wide distribution of histone H4 Lysine 16 acetylation sites and their relationship to gene expression. / Horikoshi, Nobuo; Kumar, Pankaj; Sharma, Girdhar G.; Chen, Min; Hunt, Clayton R.; Westover, Kenneth; Chowdhury, Shantanu; Pandita, Tej K.

In: Genome Integrity, Vol. 4, No. 1, 3, 12.04.2013.

Research output: Contribution to journalArticle

Horikoshi, Nobuo ; Kumar, Pankaj ; Sharma, Girdhar G. ; Chen, Min ; Hunt, Clayton R. ; Westover, Kenneth ; Chowdhury, Shantanu ; Pandita, Tej K. / Genome-wide distribution of histone H4 Lysine 16 acetylation sites and their relationship to gene expression. In: Genome Integrity. 2013 ; Vol. 4, No. 1.
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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.",
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AB - 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.

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