Biology subjects

Wolff, L.

Publications and source records attributed to Wolff, L..

3 recordsLinked to original sources

bioRxiv2020

Efficient inhibition of SARS-CoV-2 strains by a novel ACE2-IgG4-Fc fusion protein with a stabilized hinge region

The novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) enters its host cells after binding to the angiotensin-converting enzyme 2 (ACE2) via its spike glycoprotein. This interaction is critical for virus entry and virus-host membrane fusion. Soluble ACE2 ectodomains bind and neutralize the virus but the short in vivo half-lives of soluble ACE2 limits its therapeutic use. Fusion of the fragment crystallizable (Fc) part of human immunoglobulin G (IgG) to the ACE2 ectodomain can prolong the in vivo half-life but bears the risk of unwanted Fc-receptor activation and antibody-dependent disease enhancement. Here, we describe optimized ACE2-Fc fusion constructs that avoid Fc-receptor binding by using IgG4-Fc as a fusion partner. The engineered ACE2-IgG4-Fc fusion proteins described herein exhibit promising pharmaceutical properties and a broad antiviral activity at single-digit nanomolar concentration. In addition, they allow to maintain the beneficial enzymatic activity of ACE2 and thus are very promising candidate antivirals broadly acting against coronaviruses.

immunology↗

bioRxiv2020

Histone H1 protects telomeric repeats from H3K27me3 invasion in Arabidopsis

While the pivotal role of linker histone H1 in shaping nucleosome organization is well established, its functional interplays with chromatin factors along the epigenome are just starting to emerge. Here we first report that in Arabidopsis, as in mammals, H1 occupies Polycomb Repressive Complex 2 (PRC2) target genes where it favors chromatin condensation and H3K27me3 deposition. We further show that, contrasting with its conserved function in PRC2 activation at genes, H1 selectively prevents H3K27me3 accumulation at telomeres and large pericentromeric interstitial telomeric repeat (ITR) domains by restricting DNA accessibility to Telomere Repeat Binding (TRB) proteins, a group of H1-related Myb factors mediating PRC2 cis recruitment. This study unveils a mechanistic framework by which H1 avoids the formation of gigantic H3K27me3-rich domains at telomeric sequences and contributes to safeguard nucleus architecture. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/402172v5_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@13cf29dorg.highwire.dtl.DTLVardef@5c5c86org.highwire.dtl.DTLVardef@1be7516org.highwire.dtl.DTLVardef@f935cb_HPS_FORMAT_FIGEXP M_FIG Teano et al. report that that linker histone H1 and a group of H1-related telomeric proteins interplay to selectively influence the Polycomb repressive landscape at genes and telomeric repeats in Arabidopsis. These findings provide a mechanistic framework by which H1 influences the epigenome and nuclear organization in a sequence-specific manner. C_FIG HighlightsO_LIH1 promotes PRC2 activity and limits accessibility at a majority of genes C_LIO_LIH1 prevents PRC2 activity at telomeric DNA sequences C_LIO_LIPRC2 repression is achieved by restricting accessibility to TRB proteins C_LIO_LIH1 orchestrates the spatial organization of telomeres and interstitial telomeres (ITRs) C_LI

molecular biology↗

bioRxiv2020

DET1-mediated COP1 regulation avoids HY5 activity over second-site targets to tune plant photomorphogenesis

DE-ETIOLATED1 (DET1) is a negative regulator of plant photomorphogenesis acting as a component of the C3D complex, which can further associate to CULLIN4 to form a CRL4C3D E3 ubiquitin ligase. CRL4C3D is thought to act together with CRL4COP1SPA ubiquitin ligase, to promote the ubiquitin-mediated degradation of the master regulatory transcription factor ELONGATED HYPOCOTYL5 (HY5), thereby controlling photomorphogenic gene regulatory networks. Yet, functional links between COP1 and DET1 have long remained elusive. Here, upon mass spectrometry identification of DET1 and COP1-associated proteins, we provide in vivo evidence that DET1 associates with COP1 to promote its destabilization, a process necessary to dampen HY5 protein abundance. By regulating HY5 over-accumulation, DET1 is critical to avoid its association to second-site loci, including many PIF3 target genes. Accordingly, excessive HY5 levels result in an increased HY5 repressive activity and are sufficient to trigger fusca-like phenotypes otherwise observed typically in COP1 and COP9 signalosome mutant seedlings. This study therefore identifies that DET1-mediated regulation of COP1 stability tunes down HY5 cistrome and avoids hyper-photomorphogenic responses that might compromise plant viability.

plant biology↗