Identification of Rfx6 target genes involved in pancreas development and insulin translation by ChIP-seq
| Autor: | Jing Lu, Cheng Cheng, Li-Ni Song, Chang Liu, Jian-Bo Zhou, Han Shen, Jin-Kui Yang, Xiao-Rong Zhu, Jing-Yi Liu, Xi Cao, Fang-Yuan Yang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Organogenesis Biophysics Regulatory Factor X Transcription Factors Computational biology Biology Biochemistry Genome Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Insulin KEGG Pancreas Molecular Biology Gene Intron High-Throughput Nucleotide Sequencing Cell Differentiation Cell Biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis PDX1 RFX6 Chromatin immunoprecipitation Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 508:556-562 |
| ISSN: | 0006-291X |
| Popis: | Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6. We captured 4146 unique peaks in the genome region of the adult murine pancreas. Among all these binding peaks, a majority were located in intron or intergenic regions. We further annotated all peaks to their nearest gene, and over 1000 genes were captured as Rfx6-binding genes in the pancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that Rfx6-binding genes to be associated with the pancreas developmental process. A portion of selected ChIP-seq targets related with pancreas differentiation including Pdx1, Neurod1, Hnf1a, Nkx6-1, St18 and Shox2 were selected and validated as true targets by independent qPCR experiments. In addition, Rfx6 can directly bind to upstream of MiR-145, MiR-195, and possibly other non-protein-coding functional RNAs to control adult mouse pancreatic differentiation. Interestingly, our study revealed that Rfx6 played an important role in insulin translation by binding to the Eif2ak1, Upf1, and Eif5. Our data provide direct target genes of Rfx6 during pancreas development and point to Rfx6 as a potential therapeutic target for improving insulin protein content. |
| Databáze: | OpenAIRE |
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