NF90/ILF3 is a transcription factor that promotes proliferation over differentiation by hierarchical regulation in K562 erythroleukemia cells

• Published in: PloS one Vol. 13; no. 3; p. e0193126
• Main Authors: Wu, Ting-Hsuan, Shi, Lingfang, Adrian, Jessika, Shi, Minyi, Nair, Ramesh V., Snyder, Michael P., Kao, Peter N.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2018; Public Library of Science (PLoS)
• Subjects: Analysis; Base Sequence; Biology and Life Sciences; Cell Differentiation - genetics; Cell Proliferation - genetics; Chromatin; Chromatin - genetics; Chromatin - metabolism; Enhancer Elements, Genetic - genetics; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Leukemic; Humans; K562 Cells; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Nuclear Factor 90 Proteins - genetics; Nuclear Factor 90 Proteins - metabolism; Promoter Regions, Genetic - genetics; Protein Binding; Research and Analysis Methods; RNA Interference
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193126

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.