scholarly journals Transposable elements contribute to the spatiotemporal microRNA landscape in human brain development

2022 ◽  
Author(s):  
Christopher J Playfoot ◽  
Shaoline Sheppard ◽  
Evarist Planet ◽  
Didier Trono
Keyword(s):  
Transposable Elements ◽  
Human Brain ◽  
Brain Development ◽  
Mirna Expression ◽  
Web Application ◽  
Regulatory Networks ◽  
Adult Brain ◽  
Control Of Gene Expression ◽  
Human Brain Development ◽  
Gene Regulatory

Transposable elements (TEs) contribute to the evolution of gene regulatory networks and are dynamically expressed throughout human brain development and disease. One gene regulatory mechanism influenced by TEs is the miRNA system of post-transcriptional control. miRNA sequences frequently overlap TE loci and this miRNA expression landscape is crucial for control of gene expression in adult brain and different cellular contexts. Despite this, a thorough investigation of the spatiotemporal expression of TE-embedded miRNAs in human brain development is lacking. Here, we identify a spatiotemporally dynamic TE-embedded miRNA expression landscape between childhood and adolescent stages of human brain development. These miRNAs sometimes arise from two apposed TEs of the same subfamily, such as for L2 or MIR elements, but in the majority of cases stem from solo TEs. They give rise to in silico predicted high-confidence pre-miRNA hairpin structures, likely represent functional miRNAs and have predicted genic targets associated with neurogenesis. TE-embedded miRNA expression is distinct in the cerebellum when compared to other brain regions, as has previously been described for gene and TE expression. Furthermore, we detect expression of previously non-annotated TE-embedded miRNAs throughout human brain development, suggestive of a previously undetected miRNA control network. Together, as with non-TE-embedded miRNAs, TE-embedded sequences give rise to spatiotemporally dynamic miRNA expression networks, the implications of which for human brain development constitute extensive avenues of future experimental research. To facilitate interactive exploration of these spatiotemporal miRNA expression dynamics, we provide the 'Brain miRTExplorer' web application freely accessible for the community.

scholarly journals Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain

2021 ◽  
Author(s):  
Christopher J. Playfoot ◽  
Julien Duc ◽  
Shaoline Sheppard ◽  
Sagane Dind ◽  
Alexandre Coudray ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Human Brain ◽  
Brain Development ◽  
Transcriptional Activation ◽  
Protein Function ◽  
Web Application ◽  
Brain Regions ◽  
Potential Contribution ◽  
Alternative Promoters ◽  
Human Brain Development

Transposable elements (TEs) account for more than 50% of the human genome and many have been co-opted throughout evolution to provide regulatory functions for gene expression networks. Several lines of evidence suggest that these networks are fine-tuned by the largest family of TE controllers, the KRAB-containing zinc finger proteins (KZFPs). One tissue permissive for TE transcriptional activation (termed “transposcription”) is the adult human brain, however comprehensive studies on the extent of this process and its potential contribution to human brain development are lacking. To elucidate the spatiotemporal transposcriptome of the developing human brain, we have analyzed two independent RNA-seq data sets encompassing 16 brain regions from eight weeks postconception into adulthood. We reveal a distinct KZFP:TE transcriptional profile defining the late prenatal to early postnatal transition, and the spatiotemporal and cell type–specific activation of TE-derived alternative promoters driving the expression of neurogenesis-associated genes. Long-read sequencing confirmed these TE-driven isoforms as significant contributors to neurogenic transcripts. We also show experimentally that a co-opted antisense L2 element drives temporal protein relocalization away from the endoplasmic reticulum, suggestive of novel TE dependent protein function in primate evolution. This work highlights the widespread dynamic nature of the spatiotemporal KZFP:TE transcriptome and its importance throughout TE mediated genome innovation and neurotypical human brain development. To facilitate interactive exploration of these spatiotemporal gene and TE expression dynamics, we provide the “Brain TExplorer” web application freely accessible for the community.

scholarly journals Neuroserpin expression during human brain development and in adult brain revealed by immunohistochemistry and single cell RNA sequencing

2019 ◽  
Vol 235 (3) ◽  
pp. 543-554 ◽  
Author(s):  
Istvan Adorjan ◽  
Teadora Tyler ◽  
Aparna Bhaduri ◽  
Samuel Demharter ◽  
Cintia Klaudia Finszter ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Rna Sequencing ◽  
Adult Brain ◽  
Human Brain Development ◽  
Single Cell Rna Sequencing

scholarly journals Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain

2020 ◽  
Author(s):  
Christopher J. Playfoot ◽  
Julien Duc ◽  
Shaoline Sheppard ◽  
Sagane Dind ◽  
Alexandre Coudray ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Human Brain ◽  
Brain Development ◽  
Transcriptional Activation ◽  
Protein Function ◽  
Brain Regions ◽  
Potential Contribution ◽  
Alternative Promoters ◽  
Human Brain Development ◽  
Dependent Protein

AbstractTransposable elements (TEs) constitute 50% of the human genome and many have been co-opted throughout human evolution due to gain of advantageous regulatory functions controlling gene expression networks. Several lines of evidence suggest these networks can be fine-tuned by the largest family of TE controllers, the KRAB-containing zinc finger proteins (KZFPs). One tissue permissive for TE transcriptional activation (termed ‘transposcription’) is the adult human brain, however comprehensive studies on the extent of this process and its potential contribution to human brain development are lacking.In order to elucidate the spatiotemporal transposcriptome of the developing human brain, we have analysed two independent RNA-seq datasets encompassing 16 distinct brain regions from eight weeks post-conception into adulthood. We reveal an anti-correlated, KZFP:TE transcriptional profile defining the late prenatal to early postnatal transition, and the spatiotemporal and cell type specific activation of TE-derived alternative promoters driving the expression of neurogenesis-associated genes. We also demonstrate experimentally that a co-opted antisense L2 element drives temporal protein re-localisation away from the endoplasmic reticulum, suggestive of novel TE dependent protein function in primate evolution. This work highlights the widespread dynamic nature of the spatiotemporal KZFP:TE transcriptome and its potential importance throughout neurotypical human brain development.

scholarly journals A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development

2021 ◽  
Author(s):  
Pia A. Johansson ◽  
Per Ludvik Brattås ◽  
Christopher H. Douse ◽  
PingHsun Hsieh ◽  
Anita Adami ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Structural Variation ◽  
Cis Acting ◽  
Human Brain Development ◽  
Gene Regulatory

scholarly journals Human-specific genomic features of pluripotency regulatory networks link NANOG with fetal and adult brain development

2015 ◽  
Author(s):  
Gennadi V. Glinsky
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Genomic Features ◽  
Non Coding Rna ◽  
Regulatory Loci ◽  
Human Specific

AbstractGenome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically-associating domains (TADs) that are significantly enriched for HSGRL and termed rapidly-evolving in humans TADs (revTADs; Genome Biol Evol. 2016 8; 2774-88). Here, human-specific genomic features of pluripotency regulatory networks in hESC have been analyzed. The primary focus was on identification of human-specific elements of the interphase chromatin architecture of TADs responsible for transcriptional regulatory control of the NANOG, POU5F1, and POU3F2 genes. Comparative analyses of the four adjacent TADs spanning ~3.3 Mb NANOG locus-associated genomic region were carried-out to highlight primate-specific genomic features. Lastly, the putative mechanisms of the genome-wide regulatory effects of human-specific NANOG-binding sites (HSNBS) on expression of genes implicated in the fetal and adult brain development have been examined. Acquisition of primate-specific regulatory loci appears to rewire TADs exerting transcriptional control on pluripotency regulators, revealing a genomic placement pattern consistent with the enhanced regulatory impact of NANOG in primates. Proximity placement analysis of HSNBS identified a large expression signature in the human fetal neocortex temporal lobe comprising 4,957 genes, which appear to retain acquired in the embryo expression changes for many years of human brain development and maintain highly concordant expression profiles in the neocortex and prefrontal cortex regions of adult human brain. Collectively, reported herein observations indicate that genomic elements of pluripotency regulatory circuitry associated with HSNBS, specifically proteins of the classical NurD chromatin remodeling complex, contribute to transcriptional regulation of a large set of genes implicated in development and function of human brain.List of abbreviations5hmC, 5-HydromethylcytosineCTCF, CCCTC-binding factorDHS, DNase hypersensitivity sitesFHSRR, fixed human-specific regulatory regionsGRNs, genomic regulatory networksHAR, human accelerated regionshCONDEL, human-specific conserved deletionshESC, human embryonic stem cellsHSGRL, human-specific genomic regulatory lociHSNBS, human-specific NANOG-binding sitesHSTFBS, human-specific transcription factor-binding sitesLAD, lamina-associated domainLINE, long interspersed nuclear elementlncRNA, long non-coding RNALTR, long terminal repeatMADE, methylation-associated DNA editingmC, methylcytosinemESC, mouse embryonic stem cellsNANOG, Nanog homeoboxnt, nucleotidePOU5F1, POU class 5 homeobox 1PSDS, partial strand displacement stateTAD, topologically associating domainsTE, transposable elementsTF, transcription factorTSC, triple-stranded complexTSS, transcription start sitesSE, super-enhancersSED, super-enhancer domainssncRNA, small non coding RNA

scholarly journals §Using organoids to study human brain development and evolution

2021 ◽  
Author(s):  
Wai‐Kit Chan ◽  
Rana Fetit ◽  
Rosie Griffiths ◽  
Helen Marshall ◽  
John O Mason ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Development And Evolution
Sign in / Sign up

Export Citation Format

Share Document