title: Nuclear Factor I genomic binding associates with chromatin boundaries.
abstract: BACKGROUND
  The Nuclear Factor I (NFI) family of DNA binding proteins (also called CCAAT box transcription factors or CTF) is involved in both DNA replication and gene expression regulation. Using chromatin immuno-precipitation and high throughput sequencing (ChIP-Seq), we performed a genome-wide mapping of NFI DNA binding sites in primary mouse embryonic fibroblasts.
  
  
  RESULTS
  We found that in vivo and in vitro NFI DNA binding specificities are indistinguishable, as in vivo ChIP-Seq NFI binding sites matched predictions based on previously established position weight matrix models of its in vitro binding specificity. Combining ChIP-Seq with mRNA profiling data, we found that NFI preferentially associates with highly expressed genes that it up-regulates, while binding sites were under-represented at expressed but unregulated genes. Genomic binding also correlated with markers of transcribed genes such as histone modifications H3K4me3 and H3K36me3, even outside of annotated transcribed loci, implying NFI in the control of the deposition of these modifications. Positional correlation between + and - strand ChIP-Seq tags revealed that, in contrast to other transcription factors, NFI associates with a nucleosomal length of cleavage-resistant DNA, suggesting an interaction with positioned nucleosomes. In addition, NFI binding prominently occurred at boundaries displaying discontinuities in histone modifications specific of expressed and silent chromatin, such as loci submitted to parental allele-specific imprinted expression.
  
  
  CONCLUSIONS
  Our data thus suggest that NFI nucleosomal interaction may contribute to the partitioning of distinct chromatin domains and to epigenetic gene expression regulation.NFI ChIP-Seq and input control DNA data were deposited at Gene Expression Omnibus (GEO) repository under accession number GSE15844. Gene expression microarray data for mouse embryonic fibroblasts are on GEO accession number GSE15871.
authors: Institute of Biotechnology and Center for Biotecghnology UNIL-EPFL, University of Lausanne, 1015, Lausanne, Switzerland. pjanic.milos@gmail.com
authors: Milos
authors: M
authors: Pjanic
authors: Christoph D
authors: CD
authors: Schmid
authors: Armelle
authors: A
authors: Gaussin
authors: Giovanna
authors: G
authors: Ambrosini
authors: Jozef
authors: J
authors: Adamcik
authors: Petar
authors: P
authors: Pjanic
authors: Genta
authors: G
authors: Plasari
authors: Jan
authors: J
authors: Kerschgens
authors: Giovani
authors: G
authors: Dietler
authors: Philipp
authors: P
authors: Bucher
authors: Nicolas
authors: N
authors: Mermod
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002874:Chromosome Mapping; D019175:DNA Methylation; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome; D051379:Mice; D051839:NFI Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009707:Nucleosomes
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