AI Article Synopsis
- - The study explores the regulation of a complex gene locus that contains eight genes and multiple regulatory elements, including a super-enhancer, which evolved from gene duplication. - Key findings show that casein genes are significantly activated during pregnancy in mammary glands and that different genes within this locus are regulated differently; some rely on the super-enhancer, while others need additional local enhancers. - The research highlights the intricate regulatory mechanisms that allow for tissue-specific gene expression, demonstrating the interaction between enhancers and promoters in the context of mammary and salivary gland functions.
Article Abstract
Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Casein genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands, induced 10,000-fold during pregnancy and account for 50% of mRNAs during lactation, Prr27 and Fdcsp are salivary-specific and Odam has dual specificity. We probed the function of 12 candidate regulatory elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Csn1s2b, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitates activation of Csn2 during pregnancy. Our work identifies the regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435465 | PMC |
| http://dx.doi.org/10.1038/s41467-023-40712-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RNase P cleavage of pseudoknot substrates reveals differences in active site architecture that depend on residue N-1 in the 5' leader.
RNA Biol
December 2025
Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
We show that a small biotin-binding RNA aptamer that folds into a pseudoknot structure acts as a substrate for bacterial RNase P RNA (RPR) with and without the RNase P C5 protein. Cleavage in the single-stranded region in loop 1 was shown to depend on the presence of a RCCA-motif at the 3' end of the substrate. The nucleobase and the 2'hydroxyl at the position immediately 5' of the cleavage site contribute to both cleavage efficiency and site selection, where C at this position induces significant cleavage at an alternative site, one base upstream of the main cleavage site.
View Article and Find Full Text PDFGenomic and Methylomic Signatures Associated With the Maintenance of Genome Stability and Adaptive Evolution in Two Closely Allied Wolf Spiders.
Mol Ecol Resour
January 2025
Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China.
Pardosa spiders, belonging to the wolf spider family Lycosidae, play a vital role in maintaining the health of forest and agricultural ecosystems due to their function in pest control. This study presents chromosome-level genome assemblies for two allied Pardosa species, P. laura and P.
View Article and Find Full Text PDFA NAC transcription factor NAC50 regulates Fe reutilization in Arabidopsis under Fe-deficient condition.
Physiol Plant
January 2025
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Science, Nanjing, China.
A lack of iron (Fe) inhibits the growth and development of plants, leading to reduced agricultural yields and quality. In the last ten years, numerous studies have focused on the induction of Fe uptake and translocation under Fe deficiency, but the regulatory mechanisms governing Fe reutilization within plants are still not well understood. Here, we demonstrated the involvement of the NAM/ATAF1/2/CUC2 (NAC) transcription factor NAC50 in response to Fe shortage.
View Article and Find Full Text PDFDespite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding and chromatin accessibility at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA sequence model of base-resolution accessibility profiles that detects, learns and deconvolves assay-specific enzyme biases from regulatory sequence determinants of accessibility, enabling robust discovery of compact TF motif lexicons, cooperative motif syntax and precision footprints across assays and sequencing depths. Extensive benchmarks show that ChromBPNet, despite its lightweight design, is competitive with much larger contemporary models at predicting variant effects on chromatin accessibility, pioneer TF binding and reporter activity across assays, cell contexts and ancestry, while providing interpretation of disrupted regulatory syntax.
View Article and Find Full Text PDFDNA methylation patterns are inherited from the parental germline to the embryo. In mature sperm, the sites of unmethylated DNA are tightly coupled to sites of histone retention at gene regulatory elements that are implicated in paternal epigenetic inheritance. The timing and mechanism of site-specific DNA demethylation in the male germline currently remains unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!