title: Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain.
abstract: Posttranslational modification of histones through acetylation, methylation, and phosphorylation is a common mode of regulating chromatin structure and, therefore, diverse nuclear processes. One such modification, methylated histone H3 at lysine-4 (H3-meK4), colocalizes with hyperacetylated histones H3 and H4 in mammalian chromatin. Whereas activators directly recruit acetyltransferases, the process whereby H3-meK4 is established is unknown. We tested whether the hematopoietic-specific activators NF-E2 and GATA-1, which mediate transactivation of the beta-globin genes, induce both histone acetylation and H3-meK4. Through the use of NF-E2- and GATA-1-null cell lines, we show that both activators induce H3 acetylation at the promoter upon transcriptional activation. However, analysis of H3-mek4 revealed that NF-E2 and GATA-1 differentially regulate chromatin modifications at the betamajor promoter. NF-E2, but not GATA-1, induces H3-meK4 at the promoter. Thus, under conditions in which NF-E2 and GATA-1 activate the transcription of an endogenous gene at least 570-fold, these activators differ in their capacity to induce H3-meK4. Despite strong H3-meK4 at hypersensitive site 2 of the upstream locus control region, neither factor was required to establish H3-meK4 at this site. These results support a model in which multiple tissue-specific activators collectively function to assemble a composite histone modification pattern, consisting of overlapping histone acetylation and methylation. As GATA-1 induced H3 acetylation, but not H3-meK4, at the promoter, H3 acetylation and H3-meK4 components of a composite histone modification pattern can be established independently.
authors.affiliation: Molecular and Cellular Pharmacology Program, Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, 383 Medical Sciences Center, Madison, WI 53706, USA.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Kiekhaefer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Grass
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Johnson
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Boyer
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D006410:Hematopoiesis; D006657:Histones / Q000378:metabolism*; D008322:Mammals; D008745:Methylation; D051379:Mice; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D006657:Histones; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors