Integrative analysis of transcriptomic and epigenomic data reveals distinct patterns for developmental and housekeeping gene regulation

• Published in: BMC biology Vol. 22; no. 1; p. 78
• Main Authors: Abnizova, Irina, Stapel, Carine, Boekhorst, Rene Te, Lee, Jimmy Tsz Hang, Hemberg, Martin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.04.2024; BioMed Central; BMC
• Subjects: Accessibility; Analysis; Chromatin; Developmental and housekeeping genes; Developmental biology; Differentially and similarly expressed genes; DNA binding proteins; DNA methylation; Enhancers; Epigenetic inheritance; Epigenetics; Epigenomics; Gastrulation; Gene clusters; Gene expression; Gene mapping; Gene regulation; Gene regulation programs; Genes; Genetic regulation; Genetic transcription; Genomes; Health aspects; Methods; Methylation; Pioneer TFs; Promoters; Regulatory sequences; Subgroups; Transcription; Transcription activation; Transcription factors; Transcriptional architecture; Transcriptomics; United States; Differentially and similarly expressed genes; Gene regulation programs; Pioneer TFs; Epigenomics; Transcriptional architecture; Developmental and housekeeping genes
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-024-01869-2

Regulation of transcription is central to the emergence of new cell types during development, and it often involves activation of genes via proximal and distal regulatory regions. The activity of regulatory elements is determined by transcription factors (TFs) and epigenetic marks, but despite extensive mapping of such patterns, the extraction of regulatory principles remains challenging. Here we study differentially and similarly expressed genes along with their associated epigenomic profiles, chromatin accessibility and DNA methylation, during lineage specification at gastrulation in mice. Comparison of the three lineages allows us to identify genomic and epigenomic features that distinguish the two classes of genes. We show that differentially expressed genes are primarily regulated by distal elements, while similarly expressed genes are controlled by proximal housekeeping regulatory programs. Differentially expressed genes are relatively isolated within topologically associated domains, while similarly expressed genes tend to be located in gene clusters. Transcription of differentially expressed genes is associated with differentially open chromatin at distal elements including enhancers, while that of similarly expressed genes is associated with ubiquitously accessible chromatin at promoters. Based on these associations of (linearly) distal genes' transcription start sites (TSSs) and putative enhancers for developmental genes, our findings allow us to link putative enhancers to their target promoters and to infer lineage-specific repertoires of putative driver transcription factors, within which we define subgroups of pioneers and co-operators.