Establishment of a monoclonal antibody for human LXRα: Detection of LXRα protein expression in human macrophages

Watanabe, Yuichiro; Tanaka, Toshiya; Uchiyama, Y.; Takeno, Tetsu; Izumi, Atsushi; Yamashita, Hisahiko; Kumakura, Junko; Iwanari, Hiroko; Jiang, Shuying; Naito, Makoto; Mangelsdorf, David J.; Hamakubo, Takao; Kodama, Tatsuhiko

doi:10.1186/1478-1336-1-1

Cited by 22 publications

(2 citation statements)

References 24 publications

(20 reference statements)

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“…QTLs were detected using Composite Interval Mapping (CIM) in WinQTL Cartographer v2.5 [54]. Significant LOD thresholds for QTL detection were determined based on experiment-specific permutations with 1000 repeats at α = 0.05 [55]. In QTL-based epistasis analysis, the 90 RILs were categorized into sub-populations based on alleles of SbPRR37 or alleles of SbCO respectively.…”

Section: Methodsmentioning

confidence: 99%

CONSTANS is a photoperiod regulated activator of flowering in sorghum

et al. 2014

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BackgroundSorghum genotypes used for grain production in temperate regions are photoperiod insensitive and flower early avoiding adverse environments during the reproductive phase. In contrast, energy sorghum hybrids are highly photoperiod sensitive with extended vegetative phases in long days, resulting in enhanced biomass accumulation. SbPRR37 and SbGHD7 contribute to photoperiod sensitivity in sorghum by repressing expression of SbEHD1 and FT-like genes, thereby delaying flowering in long days with minimal influence in short days (PNAS_108:16469-16474, 2011; Plant Genome_in press, 2014). The GIGANTEA (GI)-CONSTANS (CO)-FLOWERING LOCUS T (FT) pathway regulates flowering time in Arabidopsis and the grasses (J Exp Bot_62:2453-2463, 2011). In long day flowering plants, such as Arabidopsis and barley, CONSTANS activates FT expression and flowering in long days. In rice, a short day flowering plant, Hd1, the ortholog of CONSTANS, activates flowering in short days and represses flowering in long days.ResultsQuantitative trait loci (QTL) that modify flowering time in sorghum were identified by screening Recombinant Inbred Lines (RILs) derived from BTx642 and Tx7000 in long days, short days, and under field conditions. Analysis of the flowering time QTL on SBI-10 revealed that BTx642 encodes a recessive CONSTANS allele containing a His106Tyr substitution in B-box 2 known to inactivate CONSTANS in Arabidopsis thaliana. Genetic analysis characterized sorghum CONSTANS as a floral activator that promotes flowering by inducing the expression of EARLY HEADING DATE 1 (SbEHD1) and sorghum orthologs of the maize FT genes ZCN8 (SbCN8) and ZCN12 (SbCN12). The floral repressor PSEUDORESPONSE REGULATOR PROTEIN 37 (PRR37) inhibits sorghum CONSTANS activity and flowering in long days.ConclusionSorghum CONSTANS is an activator of flowering that is repressed post-transcriptionally in long days by the floral inhibitor PRR37, contributing to photoperiod sensitive flowering in Sorghum bicolor, a short day plant.

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Section: Methodsmentioning

confidence: 99%

CONSTANS is a photoperiod regulated activator of flowering in sorghum

et al. 2014

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“…Its expression is regulated by either the P1 (proximal) or P2 (distal) promoter. The usage of alternate promoters and presence of alternative splicing results in up to 12 known HNF4A isoforms that are expressed in a developmental stage- and tissue-specific manner (Eeckhoute et al., 2003a, Harries et al., 2008, Huang et al., 2009, Jiang et al., 2003, Tanaka et al., 2006). Therefore HNF4A expression is dynamically regulated to ensure proper formation and function of multiple organs, in particular, the liver and pancreas (Lau et al., 2018), which are the tissues we focus on in our study.…”

Section: Introductionmentioning

confidence: 99%

HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells

Jasmen

Lim

et al. 2019

iScience

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Summary Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients.

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Nuclear localization of liver X receptor α and β is differentially regulated

Prüfer

Boudreaux

2006

J of Cellular Biochemistry

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Activity of nuclear receptors is regulated by their nuclear localization. Liver X receptors (LXR) a and b are nuclear receptors that regulate transcription of genes for cholesterol metabolism, cholesterol transport, and lipogenesis. While LXR a and b are very similar in structure and exhibit similar ligand binding properties, their physiological roles are quite different. Since the LXRs fall into a class of receptors that move between the nucleus and cytoplasm, experiments were conducted to determine whether LXR a and LXR b show differences in their nuclear localization pattern. To determine the location of each receptor, cell lines stably expressing yellow fluorescent protein (YFP) chimeras with either LXR a or LXR b were examined. Retention in the nucleus of the chimeric proteins in the presence or absence of ligands was assessed using fluorescence microscopy coupled with digitonin permeabilization assays. Surprisingly, differences were found between LXR a and LXR b. Whereas unliganded LXR a was retained in the nucleus, unliganded LXR b was partially exported. Mutations were then introduced into putative nuclear localization sequences (NLS) to determine which sequences are important for nuclear localization and function. Mutation in one such sequence abolished nuclear localization of LXR a, whereas the analogous change in LXR b had a much less dramatic effect. Mutations in analogous putative NLS also differentially affected transcriptional activation by LXR a and LXR b. These data demonstrate for the first time that nuclear retention and localization as well as function of LXR a and LXR b are differentially regulated.

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Establishment of a monoclonal antibody for human LXRα: Detection of LXRα protein expression in human macrophages

Cited by 22 publications

References 24 publications

CONSTANS is a photoperiod regulated activator of flowering in sorghum

CONSTANS is a photoperiod regulated activator of flowering in sorghum

HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells

Nuclear localization of liver X receptor α and β is differentially regulated

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