Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription.

Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries. Activation of gene expression coincides with the establishment of TADs throughout the genome and co-localization of housekeeping gene clusters, which remain stable in subsequent stages of development. However, the appearance of TAD boundaries is independent of transcription and requires the transcription factor Zelda for locus-specific TAD boundary insulation. These results offer insight into when spatial organization of the genome emerges and identify a key factor that helps trigger this architecture.

High-throughput sequencing will metamorphose the analysis of thyroid hormone receptor function during amphibian development.

Amphibian metamorphosis is marked by dramatic thyroid hormone (T(3))-induced changes including de novo morphogenesis, tissue remodeling, and organ resorption through programmed cell death. These changes involve cascades of gene regulation initiated by thyroid hormone (TH). TH functions by regulating gene expression through TH receptors (TR). TR are DNA-binding transcription factors that belong to the steroid hormone receptor superfamily. In the absence of ligand, TR can repress gene expression by recruiting a corepressor complex, whereas liganded TR recruits a coactivator complex for gene activation. Earlier studies have led us to propose a dual function model for TR during development. In premetamorphic tadpoles, unliganded TR represses transcription involving corepressors. During metamorphosis, endogenous T(3) allows TR to activate gene expression. To fully understand the diversity of T(3) effects during metamorphosis, whole genome analysis of transcriptome and mechanism of TR action should be carried out. To this end, the new sequencing technologies have dramatically changed how fundamental questions in biology are being addressed and is now making the transition from technology development to being a standard for genomic and functional genomic analysis. This review focuses on the applications of high-throughput technologies to the field of amphibian metamorphosis.