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Precision in the establishment and maintenance of cellular identities is crucial for the development of multicellular organisms and requires tight regulation of gene expression. While extensive research has focused on understanding cell type-specific gene activation, the complex mechanisms underlying the transcriptional repression of alternative fates are not fully understood. Here, we provide an overview of the repressive mechanisms involved in cell fate regulation. We discuss the molecular machinery responsible for suppressing alternative fates and highlight the crucial role of sequence-specific transcription factors (TFs) in this process. Depletion of these TFs can result in unwanted gene expression and increased cellular plasticity. We suggest that these TFs recruit cell type-specific repressive complexes to their cis-regulatory elements, enabling them to modulate chromatin accessibility in a context-dependent manner. This modulation effectively suppresses master regulators of alternative fate programs and their downstream targets. The modularity and dynamic behavior of these repressive complexes enables a limited number of repressors to canalize and maintain major and minor cell fate decisions at different stages of development. This Review discusses the key role of transcriptional repression in cell fate regulation. It provides an overview of epigenetic mechanisms and transcription factors suppressing undesired gene expression or alternative cell fates and discusses the implications for cellular reprogramming. [ABSTRACT FROM AUTHOR]

The correct wiring of neuronal circuits is one of the most complex processes in development, since axons form highly specific connections out of a vast number of possibilities. Circuit structure is genetically determined in vertebrates and invertebrates, but the mechanisms guiding each axon to precisely innervate a unique pre‐specified target cell are poorly understood. We investigated Drosophila embryonic motoneurons using single‐cell genomics, imaging, and genetics. We show that a cell‐specific combination of homeodomain transcription factors and downstream immunoglobulin domain proteins is expressed in individual cells and plays an important role in determining cell‐specific connections between differentiated motoneurons and target muscles. We provide genetic evidence for a functional role of five homeodomain transcription factors and four immunoglobulins in the neuromuscular wiring. Knockdown and ectopic expression of these homeodomain transcription factors induces cell‐specific synaptic wiring defects that are partly phenocopied by genetic modulations of their immunoglobulin targets. Taken together, our data suggest that homeodomain transcription factor and immunoglobulin molecule expression could be directly linked and function as a crucial determinant of neuronal circuit structure. Synopsis: Single‐cell RNA‐seq of Drosophila embryonic motoneurons combined with imaging and genetic perturbation suggests a linked homeodomain transcription factor – immunoglobulin program critical for synaptic wiring in the neuromuscular system. Single‐cell transcriptomes of Drosophila embryonic motoneurons were mapped along the AP axis using Hox gene expression as spatial markers.Homeodomain transcription factor (TF) and Immunoglobulin (Ig) genes were found to be highly variably expressed within twitlow motoneurons.Functional analysis suggested a regulatory and functional link between homeodomain TFs and Ig domain proteins in synaptic wiring.Common signatures of homeodomain TF expression were found in matching synaptic partners in the neuromuscular system. [ABSTRACT FROM AUTHOR]

Studying the spatiotemporal control of gene regulatory networks at the single‐cell level is still a challenge, yet it is key to understanding the mechanisms driving cellular identity. In their recent study, Aerts and colleagues (González‐Blas et al, 2020) develop a new strategy to spatially map and integrate single‐cell transcriptome and epigenome profiles in the Drosophila eye‐antennal disc and to deduce in each cell precise enhancer‐to‐gene activity relationships. This opens a new era in the transcriptional regulation field, as it allows extracting from each of the thousands of cells forming a tissue the critical features driving their identity, from enhancer sequences to transcription factors to gene regulatory networks. [ABSTRACT FROM AUTHOR]

Precise gene expression is a fundamental aspect of organismal function and depends on the combinatorial interplay of transcription factors (TFs) with cis-regulatory DNA elements. While much is known about TF function in general, our understanding of their cell type-specific activities is still poor. To address how widely expressed transcriptional regulators modulate downstream gene activity with high cellular specificity, we have identified binding regions for the Hox TF Deformed (Dfd) in the Drosophila genome. Our analysis of architectural features within Hox cis-regulatory response elements (HREs) shows that HRE structure is essential for cell type-specific gene expression. We also find that Dfd and Ultrabithorax (Ubx), another Hox TF specifying different morphological traits, interact with non-overlapping regions in vivo, despite their similar DNA binding preferences. While Dfd and Ubx HREs exhibit comparable design principles, their motif compositions and motif-pair associations are distinct, explaining the highly selective interaction of these Hox proteins with the regulatory environment. Thus, our results uncover the regulatory code imprinted in Hox enhancers and elucidate the mechanisms underlying functional specificity of TFs in vivo. [ABSTRACT FROM AUTHOR]

The article discusses the role of Hox gene as well as its structural and molecular function in morphogenesis. It says that the genes are highly conserved throughout metazoan evolution and exercise their function by activations and downstream genes. Moreover, genome wide-approach facilitates the identification of the genes. Furthermore, the morphological diversification has been driven by the representation of a step to comprehensive understanding of the Hox genes.