Fig. 4: Transcriptional regulation of LRRK2 by HIF-1α.

a Schematic linear maps of mouse LRRK2 promoter, indicating location and nucleotide sequence of four putative HRE sites and mutagenesis information of each HRE sites. b At DIV 8, pGL3-mLRRK2-Luc was transfected into primary cortical neurons, followed by scratch injury at DIV 10, and luciferase activity was measured at 48 h post-injury. Bar graph shows means ± s.d. (n = 3). c, d Primary cortical neurons were co-transfected with pGL3-mLRRK2-Luc and wild-type (WT) or dominant-negative (DN) of HIF-1α (c) or with two different siRNA against HIF-1α (d) at DIV 8. Neurons were scratched at DIV 10, and luciferase assay was performed with cell lysates at 48 h post-injury. Bar graph shows means ± s.d. (n = 4). e Primary cortical neurons were transfected with pGL3-mLRRK2-Luc or HRE mutant constructs which harbor mutations in one of the four HRE sites. Bar graph shows means ± s.d. (n = 3). f Control and scratch-injured cortical neurons were processed for chromatin immunoprecipitation (ChIP) with anti-HIF-1α or IgG control antibodies. One-way ANOVA followed by Newman–Keuls post hoc test was performed for all experiments. ***p < 0.001