Intronic enhancers regulate the expression of genes involved in tissue-specific functions and homeostasis

Acosta, Sandra

doi:10.1101/2020.08.21.260836

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Moreover, we find that recently evolved weak gE in the human lineage (hswEgE) occur in genes showing patterns of brain-specific gene expression and enriched in neuronal functions. This tissue-specific activity is consistent with what has been recently reported for gE 72 . These genes are also associated with signals of positive selection and acceleration, suggesting they may have contributed to human adaptation in several traits.…”

Section: Discussionsupporting

confidence: 92%

Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

et al. 2021

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Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.

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Section: Discussionsupporting

confidence: 92%

Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

et al. 2021

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“…Due to a hub-like position in gene regulatory networks, Bab is potentially an input-output gene that facilitates tissue-specific change (45,46). The large 5′ intergenic and intronic regions of bab in Colias and Ostrinia, and of its sub-functionalized duplicates in Drosophila, together suggest a complex cis-regulatory landscape bearing a multitude of enhancers or silencers (47)(48)(49), enabling the evolution of precise, tissue-specific changes (50). Last, the location of Bab on the lepidopteran Z chromosome is relevant to the divergence of premating traits under the assumption that sex-chromosomes are more prone to the generation of reproductive isolation than autosomes (20,51,52).…”

Section: Discussionmentioning

confidence: 99%

A genetic switch for male UV-iridescence in an incipient species pair of sulphur butterflies

Ficarrotta¹,

Jj²,

Ls³

et al. 2021

Preprint

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Mating cues evolve rapidly and can contribute to species formation and maintenance. However, little is known about how sexual signals diverge and how this variation integrates with other barrier loci to shape the genomic landscape of reproductive isolation. Here, we elucidate the genetic basis of UV iridescence, a courtship signal that differentiates the males of Colias eurytheme butterflies from a sister species, allowing females to avoid costly heterospecific matings. Anthropogenic range expansion of the two incipient species established a large zone of secondary contact across the eastern US with strong signatures of genomic admixtures spanning all autosomes. In contrast, Z chromosomes are highly differentiated between the two species, supporting a disproportionate role of sex chromosomes in speciation known as the large-X effect. Within this chromosome-wide reproductive barrier, cis-regulatory variation of bric a brac (bab) drives the male UV-iridescence polymorphism between the two species. Bab is expressed in all non-UV scales, and butterflies of either species or sex acquire widespread ectopic iridescence following its CRISPR knock-out, demonstrating that Bab functions as a suppressor of UV-scale differentiation that potentiates mating cue divergence. These results provide new insights into the diversification of sexual signals and the species concept.

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“…2D ) ( 37 ). These intronic enhancers were noted commonly to regulate genes with tissue-specific functions rather than housekeeping genes, which tend to utilize intergenic enhancers; moreover, their usage often changes during development ( 38 ). Intronic enhancer elements activate transcription strongly and are thought to affect only the gene in which they are located ( 37 ).…”

Section: Enhancers and Associated Long Non-coding Rnasmentioning

confidence: 99%

Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs

Refael

Melamed

2021

Endocrinology

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The world of long non-coding RNAs (lncRNAs) has opened up massive new prospects in understanding the regulation of gene expression. Not only are there seemingly almost infinite numbers of lncRNAs in the mammalian cell, but they have highly diverse mechanisms of action. In the nucleus, some are chromatin-associated, transcribed from transcriptional enhancers (eRNAs) and/or direct changes in the epigenetic landscape with profound effects on gene expression. The pituitary gonadotrope is responsible for activation of reproduction through production and secretion of appropriate levels of the gonadotropic hormones. As such, it exemplifies a cell whose function is defined through changes in developmental and temporal patterns of gene expression, including those that are hormonally-induced. Roles for diverse distal regulatory elements and eRNAs in gonadotrope biology have only just begun to emerge. Here, we will present an overview of the different kinds of lncRNAs that alter gene expression, and what is known about their roles in regulating some of the key gonadotrope genes. We will also review various screens that have detected differentially expressed pituitary lncRNAs associated with changes in reproductive state, and those whose expression is found to play a role in gonadotrope-derived non-functioning pituitary adenomas. We hope to shed light on this exciting new field, emphasize the open questions, and encourage research to illuminate the roles of lncRNAs in various endocrine systems.

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Intronic enhancers regulate the expression of genes involved in tissue-specific functions and homeostasis

Cited by 5 publications

References 43 publications

Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

A genetic switch for male UV-iridescence in an incipient species pair of sulphur butterflies

Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs

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