Biology subjects

Teichmann, M.

Publications and source records attributed to Teichmann, M..

4 recordsLinked to original sources

bioRxiv2025

PARP1 Regulates 3D Structure and Function of Super-Enhancers and Hormone-Control Regions in Breast Cancer Cells

Poly (ADP-ribose) polymerase 1 (PARP1) has been linked to various genomic pathways and in the maintenance of genomic stability. PARP1 has also been postulated to regulate cis-regulatory elements, but the mechanisms remain largely unknown. Here, we employed genomic approaches to show how PARP1 occupies Super-Enhancers (SEs) of luminal A T47D breast cancer cells and how some PARP1 is dynamically relodged by progesterone at hormone-control regions (HCRs). Disruption of PARP1 causes transcriptome reprogramming, altering the expression of both SE-associated and HCRs-regulated genes. This is achieved through a dual coordinated action in the establishment of long-range and intra-TADs chromatin loops, which are lost upon PARP1 ablation, but enforced by its catalytic inhibition. We show that PARP1 also plays a role in regulation of chromatin compartments. Our results reveal PARP1, as a new chromatin looper and compartments organizer controlling SEs and HCRs genes linked to cell identity and hormonal response in breast cancer cells via 3D genome organization. Highlights (Separate document)O_LIPARP1 occupies cell specific super-enhancers and hormone-control regions. C_LIO_LILoss of PARP1 alters the cell identity and progestin-induced gene expression signature. C_LIO_LIGene expression changes upon PARP1 loss relay on altered 3D chromatin looping and compartments. C_LI eTOC blurbWe have discovered that the nuclear repair protein and cancer drug target; PARP1 is preferentially bound at super-enhancers. The binding of PARP1 is essential for the underlying, cell specific gene expression program and the 3D structure of the chromatin surrounding the super-enhancer regions. Graphical abstractSeparate document O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/668155v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@1da9027org.highwire.dtl.DTLVardef@2e1966org.highwire.dtl.DTLVardef@8582eaorg.highwire.dtl.DTLVardef@155e77b_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2020

The control of plastic inhibition over excitatory synaptic plasticity leads to the joint emergence of sensory coding and contrast invariance.

Visual stimuli are represented by a highly efficient code in the primary visual cortex, but the development of this code is still unclear. Two distinct factors control coding efficiency: Representational efficiency, which is determined by neuronal tuning diversity, and metabolic efficiency, which is influenced by neuronal gain. How these determinants of coding efficiency are shaped during development, supported by excitatory and inhibitory plasticity, is only partially understood. We investigate a fully plastic spiking network of the primary visual cortex, building on phenomenological plasticity rules. Our results suggest that inhibitory plasticity is key to the emergence of tuning diversity and accurate input encoding. We show that inhibitory feedback (random and specific) increases the metabolic efficiency by implementing a gain control mechanism. Interestingly, this led to the spontaneous emergence of contrast-invariant tuning curves. Our findings highlight that (1) interneuron plasticity is key to the development of tuning diversity and (2) that efficient sensory representations are an emergent property of the resulting network.

neuroscience↗

bioRxiv2018

De-Novo-Designed Translational Repressors for Multi-Input Cellular Logic

Synthetic biology aims to apply engineering principles toward the development of novel biological systems for biotechnology and medicine. Despite efforts to expand the set of high-performing parts for genetic circuits, achieving more complex circuit functions has often been limited by the idiosyncratic nature and crosstalk of commonly utilized parts. Here, we present a molecular programming strategy that implements RNA-based repression of translation using de-novo-designed RNAs to realize high-performance orthogonal parts with mRNA detection and multi-input logic capabilities. These synthetic post-transcriptional regulators, termed toehold repressors and three-way junction (3WJ) repressors, efficiently suppress translation in response to cognate trigger RNAs with nearly arbitrary sequences using thermodynamically and kinetically favorable linear-linear RNA interactions. Automated in silico optimization of thermodynamic parameters yields improved toehold repressors with up to 300-fold repression, while in-cell SHAPE-Seq measurements of 3WJ repressors confirm their designed switching mechanism in living cells. Leveraging the absence of sequence constraints, we identify eight- and 15-component sets of toehold and 3WJ repressors, respectively, that provide high orthogonality. The modularity, wide dynamic range, and low crosstalk of the repressors enable their direct integration into ribocomputing devices that provide universal NAND and NOR logic capabilities and can perform multi-input RNA-based logic. We demonstrate these capabilities by implementing a four-input NAND gate and the expression NOT((A1 AND A2) OR (B1 AND B2)) in Escherichia coli. These features make toehold and 3WJ repressors important new classes of translational regulators for biotechnological applications.

synthetic biology↗

bioRxiv2018

TFIIIC dynamically binds Alu elements to control gene expression through chromatin looping

Folding of the mammalian genome is governed by architectural proteins, such as CTCF. TFIIIC, a RNA polymerase III transcription factor, has been identified as an insulator but its role in genome topology is totally unknown. Here, we show that TFIIIC establishes long-range genomic interactions that affect gene expression. Upon serum starvation (SS), TFIIIC occupancy increases at Alu elements (AEs) near promoters of cell cycle-related genes. Bound AEs become H3K18 hyper-acetylated and fold to contact distal pre-loaded CTCF sites near other cell cycle genes. The promoters of these genes also become hyper-acetylated ensuring their basal transcription during SS and their increased expression during serum re-exposure. Ablation of TFIIIC or deletion of the TFIIIC-bound AE that loops to the G2/M cycling F (CCNF) locus affects its expression and nuclear positioning. These results illustrate a novel function of human TFIIIC in changing 3D genome topology through the epigenetic state of AEs.\n\nHighlightsO_LISerum starvation enhances TFIIIC binding to Alu Elements (AEs) near cell cycle genes\nC_LIO_LIBinding of TFIIIC increases H3K18 acetylation over the bound AE\nC_LIO_LITFIIIC-mediated looping to distal genes favors their reactivation upon serum addition\nC_LIO_LILong-range TFIIIC interactions tune cell cycle genes expression through nuclear repositioning\nC_LI\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC=\"FIGDIR/small/455733_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (22K):\norg.highwire.dtl.DTLVardef@917ee4org.highwire.dtl.DTLVardef@21d0fborg.highwire.dtl.DTLVardef@1f1a17org.highwire.dtl.DTLVardef@1e9df24_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗