Nuclear Factor I genomic binding associates with chromatin boundaries

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsOur 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.

Nuclear factor one transcription factors as epigenetic regulators in cancer

“…More recently, genome wide mapping analysis of NFI DNA binding sites within mouse embryonic fibroblasts confirms that there is a clear association between NFI and histone H3 . Consistent with this, NFI globally associates with chromatin domain boundaries, separating permissive and silent chromatin markers as defined by localization with H3K27me3 and H3K36me3 boundaries of opposite polarities, and they were further found to directly interact with positioned nucleosomes …”

“…NFIB has been shown to directly repress EZH2 during development of the cerebral cortex to promote neuronal differentiation. 59 The genomewide mapping study previously discussed by Pjanic and colleagues 43 correlated NFI with histone methylation modifications H3K4me3 and H3K36me3 at markers of transcribed genes and even outside annotated transcribed loci, suggesting that NFIs may facilitate these modifications. NFIs have also been shown to interact with histone deacetylases, such as BAF, at various promoter regions 60,61 and other transcriptional activators such as BRG1.…”

Differential DNA methylation of vocal and facial anatomy genes in modern humans

“…Interestingly, NFI proteins were shown to bind the upstream enhancers of SOX9 (ref. 38 ), hence suggesting a possible mechanism to the simultaneous changes in the five top genes we report.…”

“…Unlike tools that use GO terms or RNA expression data, Gene ORGANizer is based entirely on curated gene-disease and gene-phenotype associations from monogenic diseases. It relies on direct phenotypic observations in human patients whose conditions are associated with known gene 38,014,016,197). This is an example of a lineage-specific DMR, defined as a locus in which all samples of a group are found outside the range of methylation in the other groups.…”

The ChIP-Seq tools and web server: a resource for analyzing ChIP-seq and other types of genomic data

“…Chippeak is at least 10 times faster than any other ChIP-seq peak finder we have tested (Additional file 1: Table S3). In spite of its simplicity, it generally performs well, sometimes even better than competing programs using a more elaborate statistical model to assess the significance of a peak [22, 23]. …”