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Adipocyte-Specific ATAC-Seq with Adipose Tissues Using Fluorescence-Activated Nucleus Sorting
Published on: March 17, 2023
Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα
Tengfei Xiao1, Lihui Liu2, Hongling Li3
1Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA 02215, USA.
Abstract:
C/EBPα is a critical transcriptional regulator of adipogenesis. How C/EBPα transcription is itself regulated is poorly understood, however, and remains a key question that needs to be addressed for a complete understanding of adipogenic development. Here, we identify a lncRNA, ADINR (adipogenic differentiation induced noncoding RNA), transcribed from a position ∼450 bp upstream of the C/EBPα gene, that orchestrates C/EBPα transcription in vivo. Depletion of ADINR leads to a severe adipogenic defect that is rescued by overexpression of C/EBPα. Moreover, we reveal that ADINR RNA specifically binds to PA1 and recruits MLL3/4 histone methyl-transferase complexes so as to increase H3K4me3 and decrease H3K27me3 histone modification in the C/EBPα locus during adipogenesis. These results show that ADINR plays important roles in regulating the differentiation of human mesenchymal stem cells into adipocytes by modulating C/EBPα in cis.
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