Abstract
NF90 and splice variant NF110 are DNA- and RNA-binding proteins encoded by the Interleukin enhancer-binding factor 3 (ILF3) gene that have been established to regulate RNA splicing, stabilization and export. The roles of NF90 and NF110 in regulating transcription as chromatin-interacting proteins have not been comprehensively characterized. Here, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) identified 9,081 genomic sites specifically occupied by NF90/NF110 in K562 cells. One third of NF90/NF110 peaks occurred at promoters of annotated genes. NF90/NF110 occupancy colocalized with chromatin marks associated with active promoters and strong enhancers. Comparison with 150 ENCODE ChIP-seq experiments revealed that NF90/NF110 clustered with transcription factors exhibiting preference for promoters over enhancers (POLR2A, MYC, YY1). Differential gene expression analysis following shRNA knockdown of NF90/NF110 in K562 cells revealed that NF90/NF110 activates transcription factors that drive growth and proliferation (EGR1, MYC), while attenuating differentiation along the erythroid lineage (KLF1). NF90/NF110 associates with chromatin to hierarchically regulate transcription factors that promote proliferation and suppress differentiation.
Highlights
Eukaryotic gene expression depends on tight and dynamic regulation of RNA transcription
(hg19) reference genome from K562 experiments deposited by various Encyclopedia of DNA Elements (ENCODE)-affiliated groups allowed us to integrate our ChIP-seq analysis with studies on chromatin landscape, transcription factor occupancy, and gene expression analysis of the K562 genome to elucidate the role of Nuclear Factor 90 (NF90)/NF110 in regulating gene expression in the context of diverse combinatorial events on the chromatin
Over 9,000 recovered NF90/NF110 peaks were consistent across Irreproducible Discovery Rate (IDR) analysis of biological replicates (Fig 1A) (S1 Table)
Summary
Eukaryotic gene expression depends on tight and dynamic regulation of RNA transcription. Transcription of RNA occurs pervasively, and is critically modulated by nucleic acid-binding proteins at the levels of epigenetic control of chromatin landscape, transcription of the genome from DNA into RNA, and regulated stability of the resulting transcript [1]. Dynamic regulation of gene expression confers organismal diversity [2], cell-type complexity [3], and underlies the immediate early response of a cell upon activation by external stimuli [4]. NF90/ILF3 ChIP-seq reveals transcriptional activation role in K562 cells cgi-bin/hgTracks?hgS_doOtherUser= submit&hgS_otherUserName=peterkao&hgS_ otherUserSessionName=thsuanwu_ILF3ChIP_ 20170807
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