Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch

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Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 ( ...

During gastrulation, Hox genes are activated in a timesequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated wit ...

The adaptation of organisms to their environment depends on the innovative potential inherent to genetic variation. In complex organisms such as mammals, processes like development and immunity require tight gene regulation. Complex forms emerge more often ...

Since Strahl and Allis proposed the "language of covalent histone modifications", a host of experimental studies have shed light on the different facets of chromatin regulation by epigenetic mechanisms. Initially proposed as a concept for controlling gene ...

Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been di ...

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify al ...

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed tr ...

Two fundamental properties of embryonic stem cells (ESCs) are their ability to self-renew and differentiate into all somatic cell types. Maintenance of their identity faces major challenges when transitioning through mitosis, as most DNA-binding proteins a ...

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

Mutations to gene regulatory networks can be maladaptive or a source of evolutionary novelty. Epistasis con-founds our understanding of how mutations affect the expression patterns of gene regulatory networks, a chal-lenge exacerbated by the dependence of ...

Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated ...

BackgroundIt is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid conten ...

X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved concom ...

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

Whole genome doubling (WGD) events are drivers of genetic innovation across vertebrate evolution. While generally detrimental to mammalian organisms, WGDs are crucial in the development of various plants and fungi, as well as for the terminal differentiati ...

Understanding how biological matter takes its shape is instrumental to biology, bioengineering, medicine, and bioinspired engineering. Gaining information on the principles of morphogenesis could enable clinicians to correct developmental abnormalities, ev ...

In vertebrate embryos, the elongating body axis is patterned via the sequential and rhyth-mic production of segments from a posterior unsegmented tissue called the presomitic mesoderm (PSM). This process is controlled by a population of cellular oscillator ...

A key player in the formation of endoplasmic reticulum sheets is CLIMP-63, but mechanistic details remained elusive. Here authors combined cellular experiments and mathematical modelling to show that S-acylation of CLIMP-63 regulates its function by mediat ...

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

Here the authors show that a strong enhancer sequence can be controlled by the chromatin environment provided by a topologically associated domain (TAD) located nearby. An enhancer relocated by homologous recombination takes all the hallmarks of its new ne ...

Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch

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