Flightless-I homolog regulates glucocorticoid receptor-mediated transcription via direct interaction of the leucine-rich repeat domain
- Authors
- Jin, Hong Lan; Yang, Liu; Jeong, Kwang Won
- Issue Date
- Apr-2017
- Publisher
- SPRINGER
- Keywords
- FLII; Glucocorticoid receptor; Leucine-rich repeat; Nuclear receptor; CARM1; P300
- Citation
- MOLECULAR BIOLOGY REPORTS, v.44, no.2, pp.243 - 250
- Journal Title
- MOLECULAR BIOLOGY REPORTS
- Volume
- 44
- Number
- 2
- Start Page
- 243
- End Page
- 250
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6280
- DOI
- 10.1007/s11033-017-4106-3
- ISSN
- 0301-4851
- Abstract
- Flightless-I homolog (FLII) is a member of the gelsolin family of proteins, and has been identified as a coactivator of estrogen receptor-mediated transcription. Here, we investigate the role of FLII in the glucocorticoid receptor (GR) signaling pathway. Reporter gene assay and real-time quantitative PCR in A549 were performed to investigate the function of FLII in the expression of GR target genes. Co-immunoprecipitation assay and in vitro binding assay were used to identify binding domain of FLII. Chromatin immunoprecipitation assay were carried out with FLII-depleted A549 cells to determine the role of FLII at GR binding sites. We demonstrate that FLII potentiates GR-mediated reporter gene activity synergistically with CARM1 and p300 to enhance GR transcriptional activity in the presence of dexamethasone (Dex) in A549 cells. Depletion of endogenous FLII inhibited the expression of Dex-regulated GR target genes in A549 cells, indicating that FLII is required for GR-mediated transcription. Further, we observed that FLII binds to GR via its N-terminal leucine-rich repeat (LRR) region, suggesting that the enhancement of GR activation may occur through the interaction of GR and FLII. Moreover, chromatin immunoprecipitation analysis demonstrated that FLII is recruited to the GR binding sites. In addition, depletion of endogenous FLII decreased the recruitment of p300, and subsequently RNA polymerase II, to specific sites of GR target genes. Taken together, these studies reveal a functional involvement of FLII in activating transcription of GR target genes, suggesting a physiological role for FLII in the GR signaling pathway.
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