Biology subjects

Ermakova, O.

Publications and source records attributed to Ermakova, O..

3 recordsLinked to original sources

bioRxiv2018

The Hox Transcription Factor Ubx stabilizes Lineage Commitment by Suppressing Cellular Plasticity

During development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei of Drosophila embryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.

developmental biology↗

bioRxiv2018

WEADE: a workflow for enrichment analysis and data exploration

Data analysis based on enrichment of Gene Ontology terms has become an important step in exploring large gene or protein expression datasets and several stand-alone or web tools exist for that purpose. However, a comprehensive and consistent analysis downstream of the enrichment calculation is missing so far. With WEADE we present a free web application that offers an integrated workflow for the exploration of genomic data combining enrichment analysis with a versatile set of tools to directly compare and intersect experiments or candidate gene lists of any size or origin including cross-species data. Lastly, WEADE supports the graphical representation of output data in the form of functional interaction networks based on prior knowledge, allowing users to go from plain expression data to functionally relevant candidate sub-lists in an interactive and consistent manner.

bioinformatics↗

bioRxiv2017

Decoding the regulatory logic of the Drosophila male stem cell system

In the past decade, the importance of the niche to provide regulatory inputs to balance stem cell self-renewal and differentiation has become clear. However, the regulatory interplay between stem cells and their niche at the whole genome level is still poorly understood. To elucidate the mechanisms controlling stem cells and their progenies as they progress through their developmental program at the transcriptional level, we recorded the regulatory program of two independent cell lineages in the Drosophila testis stem cell model. To this end, we identified genes active in the soma or germline as well as genome-wide binding profiles of two essential transcription factors, Zfh-1 and Abd-A, expressed in somatic support cells and crucial for fate acquisition of both cell lineages. Our data identified key roles for TOR signalling, signal processing V-ATPase proton pumps and the nuclear transport engaged nucleoporins and we demonstrate their importance in controlling germline maintenance, proliferation and differentiation from the support side. To make our dataset publicly available and support quick and intuitive data mining, we generated an interactive online analysis tool. Applying our tool for comparative analysis, we uncovered conserved core gene sets of adult stem cells across species boundaries. We have tested the functional relevance of these genes in the Drosophila testis and intestine and find a striking overrepresentation of stem cell defects when the corresponding genes were depleted. In summary, our dataset and interactive platform represents a versatile tool for identifying novel gene networks active in diverse stem cell types and provides a valuable resource for elucidating the multifaceted regulatory inputs required to guide proper stem cell behaviour.

developmental biology↗