Super-enhancer-associated transcription factors maintain transcriptional regulation in mature podocytes

Jingping Yang*, Difei Zhang, Masaru Motojima, Tsutomu Kume, Qing Hou, Yu Pan, Aiping Duan, Mingchao Zhang, Song Jiang, Jinhua Hou, Jingsong Shi, Zhaohui Qin, Zhihong Liu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background Transcriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood. Methods The distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance. Results Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish. Conclusions FOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs' regulatory roles in glomeruli transcription programs.

Original languageEnglish (US)
Pages (from-to)1323-1337
Number of pages15
JournalJournal of the American Society of Nephrology
Issue number6
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Nephrology


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