Biology subjects

Straub, T.

Publications and source records attributed to Straub, T..

3 recordsLinked to original sources

bioRxiv2018

Cell type-specific complement expression from healthy and diseased retinae

Retinal degeneration is associated with complement system activation, but retinal sources of complement are unknown. Here, we describe the human and murine complement transcriptomes of Muller cells, microglia/macrophages, vascular cells, neurons and retinal pigment epithelium (RPE) in health and disease. All cell populations expressed c1s, c3, cfb, cfp, cfh and cfi. Murine Muller cells contributed the highest amount of complement activators (c1s, c3, cfb). RPE mainly expressed cfh, while cfi and cfp transcripts were most abundant in neurons. The main complement negative regulator in the human retina was cfi, while cfh dominated in the murine retina. Importantly, the expression of c1s, cfb, cfp, cfi increased and that of cfh decreased with aging. Impaired photoreceptor recycling led to an enhanced c3 expression in RPE and to a reduced cfi expression in microglia/macrophages. Expression of complement components was massively upregulated after transient retinal ischemia in murine microglia, Muller cells and RPE. The individual signature of complement expression in distinct murine and human retinal cell types indicates a local, well-orchestrated regulation of the complement system in both species.

neuroscience↗

bioRxiv2017

CHRAC/ACF Contribute to the Repressive Ground State of Chromatin

The chromatin remodeling complexes CHRAC and ACF combine the ATPase ISWI with the signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro, but how their actions affect physiological gene expression is unclear. Here we explored the influence of Drosophila CHRAC/ACF on transcription by complementary gain- and loss-of-function approaches.\n\nTargeting ACF1 to multiple reporter genes inserted at many different genomic locations revealed a context-dependent inactivation of poorly transcribed reporters in repressive chromatin. Accordingly, single-embryo transcriptome analysis of a Acf knock-out allele showed that only lowly expressed genes are de-repressed in the absence of ACF1. Finally, the nucleosome arrays in Acf-deficient chromatin show loss of physiological regularity, particularly in transcriptionally inactive domains.\n\nTaken together our results highlight that ACF1-containing remodeling factors contribute to the establishment of an inactive ground state of the genome through chromatin organization.

molecular biology↗

bioRxiv2016

Genome-wide analysis of phased nucleosomal arrays reveals the functional characteristic of the nucleosome remodeler ACF

Regular successions of positioned nucleosomes - phased nucleosome arrays (PNAs) - are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.

molecular biology↗