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Results for “cis-regulatory element”

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40 records · Page 3

Temporal regulation of cold transcriptional response in switchgrass

Switchgrass low-land ecotypes have significantly higher biomass but lower cold tolerance compared to up-land ecotypes. Understanding the molecular mechanisms underlying cold response, including the ones at transcriptional level, can contribute to improving tolerance of high-yield switchgrass under chilling and freezing environmental conditions. Here, by analyzing an existing switchgrass transcriptome dataset, the temporal cis- regulatory basis of switchgrass transcriptional response to cold is dissected computationally. We found that the number of cold-responsive genes and enriched Gene Ontology terms increased as duration of cold treatment increased from 30 min to 24 hours, suggesting an amplified response/cascading effect in cold-responsive gene expression. To identify genomic sequences likely important for regulating cold response, machine learning models predictive of cold response were established using k -mer sequences enriched in the genic and flanking regions of cold-responsive genes but not non-responsive genes. These k -mers, referred to as putative cis -regulatory elements (pCREs) are likely regulatory sequences of cold response in switchgrass. There are in total 655 pCREs where 54 are important in all cold treatment time points. Consistent with this, eight of 35 known cold-responsive CREs were similar to top-ranked pCREs in the models and only these eight were important for predicting temporal cold response. More importantly, most of the top-ranked pCREs were novel sequences in cold regulation. Our findings suggest additional sequence elements important for cold-responsive regulation previously not known that warrant further studies.

60 APPLIED LIFE SCIENCES↗

A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

59 BASIC BIOLOGICAL SCIENCES↗

Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases.

59 BASIC BIOLOGICAL SCIENCES↗

Helper-embedded satellites from an integrase clade that repeatedly targets prophage late genes

Abstract Satellites such as phage-induced chromosomal islands (PICIs) are mobile genetic elements relying on helper phages for their mobilization, through trans-regulatory interactions. We discovered a PICI with a more intimate cis-regulatory configuration, integrated within a late gene of its helper prophage. This helper-embedded PICI (HE-PICI) configuration delays expression of the interrupted helper late gene until the satellite excises and provides passive helper-driven components to both HE-PICI replication and late transcription. Upon induction of a helper-satellite composite, precise excision of the entire composite was observed, followed by composite replication, then satellite excision. We mapped 491 additional HE-PICIs to one of 14 sites in cognates of phage lambda late genes. Associated integrases form a single phylogenetic clade with subclades respecting the 14 site groups, exhibiting repeated tropism for prophage late genes as new integration sites evolve. Four ordered zones in a general gram-negative PICI genome organization are: an integration zone encoding integrase and AlpA, a dynamic zone encoding members of the Bro-N network of domain-swapping DNA-interactive proteins and immunity repressor RNAs, a replication zone, and a dynamic late zone in which clusters as large as 17 consecutive helper prophage late genes have been captured. Helper-embedded satellites present new dimensions in satellite/helper relationships.

Tommasini, Dario↗