Biology subjects

Fossat, N.

Publications and source records attributed to Fossat, N..

3 recordsLinked to original sources

bioRxiv2020

TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation

Protein interaction is critical molecular regulatory activity underlining cellular functions and precise cell fate choices. Using TWIST1 BioID-proximity-labelling and network propagation analyses, we discovered and characterized a TWIST-chromatin regulatory module (TWIST1-CRM) in the neural crest cell (NCC). Combinatorial perturbation of core members of TWIST1-CRM: TWIST1, CHD7, CHD8, and WHSC1 in cell models and mouse embryos revealed that loss of the function of the regulatory module resulted in abnormal specification of NCCs and compromised craniofacial tissue patterning. Our results showed that in the course of cranial neural crest differentiation, phasic activity of TWIST1 and the interacting chromatin regulators promote the choice of NCC fate while suppressing neural stem cell fates, and subsequently enhance ectomesenchyme potential and cell motility. We have revealed the connections between TWIST1 and potential neurocristopathy factors which are functionally interdependent in NCC specification. Moreover, the NCC module participate in the genetic circuit delineating dorsal-ventral patterning of neural progenitors in the neuroepithelium.

developmental biology↗

bioRxiv2019

TWIST1 homo- and heterodimers orchestrate specificity control in embryonic stem cell lineage differentiation and craniofacial development

The extensive array of bHLH transcription factors and their combinations as dimers underpin the diversity of molecular function required for cell type specification during embryogenesis. The bHLH factor TWIST1 plays pleiotropic roles during development. However, which combinations of TWIST1 dimers are involved and what impact each dimer imposes on the gene regulation network controlled by TWIST1 remain elusive. In this work, proteomic profiling of human-TWIST1 expressing cell lines and transcriptome analysis of mouse cranial mesenchyme have revealed that TWIST1 homodimer and heterodimers with TCF3, TCF4 and TCF12 E-proteins are the predominant dimer combinations. Dimers formation or their balance are altered by disease-causing mutations in TWIST1 helix domains, which may account for the defective differentiation of the craniofacial mesenchyme observed in patients. Functional analyses of the loss and gain of TWIST1-E-protein dimer activity have revealed previously unappreciated roles in guiding lineage differentiation of embryonic stem cells: TWIST1-E-protein heterodimers activate the differentiation of mesoderm and neural crest cells which is accompanied by epithelial-to-mesenchymal transition, while TWIST1 homodimers maintain the stem cells in a progenitor state and block entry to the endoderm lineage.

developmental biology↗

bioRxiv2018

Ularcirc: Visualisation and enhanced analysis of circular RNAs via back and canonical forward splicing

Circular RNAs (circRNAs) are a unique class of transcripts that can only be identified from sequence alignments spanning discordant junctions, commonly referred to as backsplice junctions (BSJ). The challenges of detecting a BSJ from short read high throughput sequencing (HTS) data has steered software development to focus primarily on algorithmic methods to accurately capture BSJs. Here we present Ularcirc, the first software tool that provides a complete circRNA workflow from detection, integrated visualization, quality filtering of BSJ and forward splicing junctions (FSJ), through to sequence retrieval and downstream functional analysis. More importantly, Ularcirc uses an innovative method to filter out false positive circRNAs coined read alignment distribution (RAD) score which allows detection of circRNAs independent of gene annotations. We used Ularcirc to characterise circRNAs from public and in-house generated data sets and demonstrate how to discover (i) novel splicing patterns of parental transcripts, (ii) internal splicing patterns of circRNA, and (iii) the complexity of BSJ formation. Furthermore, we identify circRNAs that have potential open reading frames longer than their linear sequence. Finally, we have identified and validated the presence of a novel class of circRNA generated from ApoA4 transcripts whose BSJ derive from multiple sites within coding exons. Ularcirc can be accessed via https://github.com/VCCRI/Ularcirc.

bioinformatics↗