Molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression

Nephrin plays a key role in maintaining the structure of the slit diaphragm in the glomerular filtration barrier. Our previous studies have demonstrated potent renoprotective activity for 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)). Here we showed that in podocytes 1,25(OH)(2)D(3) markedly stimulated nephrin mRNA and protein expression. ChIP scan of the 6-kb 5' upstream region of the mouse nephrin gene identified several putative vitamin D response elements (VDREs), and EMSA confirmed that the VDRE at -312 (a DR4-type VDRE) could be bound by vitamin D receptor (VDR)/retinoid X receptor. Luciferase reporter assays of the proximal nephrin promoter fragment (-427 to +173) showed strong induction of luciferase activity upon 1,25(OH)(2)D(3) treatment, and the induction was abolished by mutations within -312VDRE. ChIP assays showed that, upon 1,25(OH)(2)D(3) activation, VDR bound to this VDRE leading to recruitment of DRIP205 and RNA polymerase II and histone 4 acetylation. Treatment of mice with a vitamin D analog induced nephrin mRNA and protein in the kidney, accompanied by increased VDR binding to the -312VDRE and histone 4 acetylation. 1,25(OH)(2)D(3) reversed high glucose-induced nephrin reduction in podocytes, and vitamin D analogs prevented nephrin decline in both type 1 and 2 diabetic mice. Together these data demonstrate that 1,25(OH)(2)D(3) stimulates nephrin expression in podocytes by acting on a VDRE in the proximal nephrin promoter. Nephrin up-regulation likely accounts for part of the renoprotective activity of vitamin D.     

Nucleosome destabilization in the epigenetic regulation of gene expression

Assembly, mobilization and disassembly of nucleosomes can influence the regulation of gene expression and other processes that act on eukaryotic DNA. Distinct nucleosome-assembly pathways deposit dimeric subunits behind the replication fork or at sites of active processes that mobilize pre-existing nucleosomes. Replication-coupled nucleosome assembly appears to be the default process that maintains silent chromatin, counteracted by active processes that destabilize nucleosomes. Nucleosome stability is regulated by the combined effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent nucleosome remodellers, post-translational modifications and histone variants. Recent studies suggest that histone turnover helps to maintain continuous access to sequence-specific DNA-binding proteins that regulate epigenetic inheritance, providing a dynamic alternative to histone-marking models for the propagation of active chromatin.     

Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome

Background

Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability.

Methods

we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation.

Results

We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression.

Conclusion

The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.     

Sugar regulation of gene expression in plants

The molecular details of sugar sensing and sugar-mediated signal transduction pathways are unclear but recent results suggest that hexokinase functions as an important plant sugar sensor in a way that is similar to that found in yeast. The use of mutants in Arabidopsis defective in specific signaling steps is of particular importance because these give access to the genes encoding components in the signaling pathways. In addition, the physiological analysis of such mutants may reveal the interaction of sugar-induced signaling pathways and those induced by other stimuli such as environmental or biotic stress.     

MicroRNA regulation of gene expression in plants

It has only been a few years since we began to appreciate that microRNAs provide an unanticipated level of gene regulation in both plants and metazoans. The high level of complementarity between plant microRNAs and their target mRNAs has allowed rapid progress towards the elucidation of their varied biological functions. MicroRNAs have been shown to regulate diverse developmental processes, including organ separation, polarity, and identity, and to modulate their own biogenesis and function. Recently, they have also been implicated in some processes outside of plant development.     

Phytochrome regulation of nuclear gene expression in plants

The photoregulation of gene expression in higher plants was extensively studied during the 1980s, in particular the light-responsive cis -acting elements and trans -acting factors of the Lhcb and rbcS genes. However, little has been discovered about: (1) which plant genes are regulated by light, and (2) which photoreceptors control the expression of these genes. In the 1990s, the functional analysis of the various photoreceptors has progressed rapidly using photoreceptor-deficient mutants, including those of the phytochrome gene family. More recently however, advanced techniques for gene expression analysis, such as fluorescent differential display and DNA microarray technology, have become available enabling the global identification of genes that are regulated by particular photoreceptors. In this paper we describe distinct and overlapping effects of individual phytochromes on gene expression in Arabidopsis thaliana.