title: Selective requirement of H2B N-Terminal tail for p14ARF-induced chromatin silencing.
abstract: The N-terminal tail of histone H2B is believed to be involved in gene silencing, but how it exerts its function remains elusive. Here, we report the biochemical characterization of p14ARF tumor suppressor as a transcriptional repressor that selectively recognizes the unacetylated H2B tails on nucleosomes. The p14ARF-H2B tail interaction is functional, as the antagonistic effect of p14ARF on chromatin transcription is lost upon deletion or acetylation of H2B tails. Gene expression profiling and chromatin immunoprecipitation studies emphasize the significance of H2B deacetylation and p14ARF recruitment in establishing a repressive environment over the cell cycle regulatory genes. Moreover, HDAC1-mediated H2B deacetylation, especially at K20, constitutes an essential step in tethering p14ARF near target promoters. Our results thus reveal a hitherto unknown role of p14ARF in the regulation of chromatin transcription, as well as molecular mechanisms governing the repressive action of p14ARF.
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Jongkyu
authors.initials: J
authors.lastname: Choi
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Kim
authors.forename: Kyunghwan
authors.initials: K
authors.lastname: Kim
authors.forename: Bomi
authors.initials: B
authors.lastname: Lee
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
authors.forename: Woojin
authors.initials: W
authors.lastname: An
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000235:genetics*; D020868:Gene Silencing; D018816:Genes, cdc; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D051057:Proto-Oncogene Proteins c-akt; D056284:Histone Deacetylase 1