Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional analysis of human and chimpanzee promoters.

ABSTRACT:

Background

It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues.

Results

Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues.

Conclusion

Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.

SUBMITTER: Heissig F

PROVIDER: S-EPMC1175988 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Functional analysis of transcription factor binding sites in human promoters.

Project description:BackgroundThe binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1.ResultsIn each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif.ConclusionsThe genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions.

| S-EPMC3491394 | biostudies-literature

Functional analysis of the human annexin I and VI gene promoters.

Project description:To gain insight into the molecular basis of annexin gene expression we have analysed the annexin I and VI gene promoters. A previously described 881 bp sequence immediately upstream of the annexin I transcription start site and a similar size fragment proximal to the annexin VI transcription start site both drove expression of the luciferase reporter gene in fibroblasts and epithelial cells. Neither promoter displayed any sensitivity to dexamethasone, suggesting that the putative glucocorticoid response element in the annexin I promoter is non-functional. Consistent with this, endogenous annexin I gene expression was unaffected by dexamethasone at the mRNA and protein levels in A431 cells. A series of 5' deletions of the two promoters were examined to define the minimal active sequences. For annexin I this corresponded to a sequence approx. 150 bp upstream of the transcription start site that included CAAT and TATA boxes. Unexpectedly, the annexin VI promoter, which also contains CAAT and TATA boxes, was fully active in the absence of these elements, a 53 bp sequence between these boxes and the transcription start site having maximal activity. Electrophoretic mobility-shift assays with nuclear extracts from A431 and HeLa cells with probes corresponding to this region revealed an SP1-binding site. These results show that the annexin I and VI genes have individual modes of transcriptional regulation and that if either annexin I or annexin VI has an anti-inflammatory role, then this is in the absence of steroid-induced gene expression.

| S-EPMC1219528 | biostudies-other

Comparative Functional Morphology of Human and Chimpanzee Feet Based on Three-Dimensional Finite Element Analysis.

Project description:To comparatively investigate the morphological adaptation of the human foot for achieving robust and efficient bipedal locomotion, we develop three-dimensional finite element models of the human and chimpanzee feet. Foot bones and the outer surface of the foot are extracted from computer tomography images and meshed with tetrahedral elements. The ligaments and plantar fascia are represented by tension-only spring elements. The contacts between the bones and between the foot and ground are solved using frictionless and Coulomb friction contact algorithms, respectively. Physiologically realistic loading conditions of the feet during quiet bipedal standing are simulated. Our results indicate that the center of pressure (COP) is located more anteriorly in the human foot than in the chimpanzee foot, indicating a larger stability margin in bipedal posture in humans. Furthermore, the vertical free moment generated by the coupling motion of the calcaneus and tibia during axial loading is larger in the human foot, which can facilitate the compensation of the net yaw moment of the body around the COP during bipedal locomotion. Furthermore, the human foot can store elastic energy more effectively during axial loading for the effective generation of propulsive force in the late stance phase. This computational framework for a comparative investigation of the causal relationship among the morphology, kinematics, and kinetics of the foot may provide a better understanding regarding the functional significance of the morphological features of the human foot.

| S-EPMC8793834 | biostudies-literature

Characterization and potential functional significance of human-chimpanzee large INDEL variation.

Project description:BackgroundAlthough humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL) variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp) may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression.ResultsExtensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them.ConclusionsThe results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

| S-EPMC3215961 | biostudies-literature

Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters.

Project description:Given the inherent limitations of in silico studies relying solely on DNA sequence analysis, the functional characterization of mammalian promoters and associated cis-regulatory elements requires experimental support, which demands cloning and analysis of putative promoter regions. Focusing on human chromosome 21, we cloned 182 gene promoters of 2500 bp in length and conducted reporter gene assays on transfected-cell arrays. We found 56 promoters that were active in HEK293 cells, while another 49 promoters could be activated by treatment of cells with Trichostatin A or depletion of serum. We observed high correlations between promoter activities and endogenous transcript levels, RNA polymerase II occupancy, CpG islands and core promoter elements. Truncation of a subset of 62 promoters to ∼500 bp revealed that truncation rarely resulted in loss of activity, but rather in loss of responses to external stimuli, suggesting the presence of cis-regulatory response elements within distal promoter regions. In these regions, we found a strong enrichment of transcription factor binding sites that could potentially activate gene expression in the presence of stimuli. This study illustrates the modular functional architecture of chromosome 21 promoters and helps to reveal the complex mechanisms governing transcriptional regulation.

| S-EPMC2952857 | biostudies-literature

Zinc-finger transcription factors are associated with guanine quadruplex motifs in human, chimpanzee, mouse and rat promoters genome-wide.

Project description:Function of non-B DNA structures are poorly understood though several bioinformatics studies predict role of the G-quadruplex DNA structure in transcription. Earlier, using transcriptome profiling we found evidence of widespread G-quadruplex-mediated gene regulation. Herein, we asked whether potential G-quadruplex (PG4) motifs associate with transcription factors (TF). This was analyzed using 220 position weight matrices [designated as transcription factor binding sites (TFBS)], representing 187 unique TF, in >75,000 genes in human, chimpanzee, mouse and rat. Results show binding sites of nine TFs, including that of AP-2, SP1, MAZ and VDR, occurred significantly within 100 bases of the PG4 motif (P < 1.24E-10). PG4-TFBS combinations were conserved in 'orthologously' related promoters across all four organisms and were associated with >850 genes in each genome. Remarkably, seven of the nine TFs were zinc-finger binding proteins indicating a novel characteristic of PG4 motifs. To test these findings, transcriptome profiles from human cell lines treated with G-quadruplex-specific molecules were used; 66 genes were significantly differentially expressed across both cell-types, which also harbored conserved PG4 motifs along with one/more of the nine TFBS. In addition, genes regulated by PG4-TFBS combinations were found to be co-regulated in human tissues, further emphasizing the regulatory significance of the associations.

| S-EPMC3185432 | biostudies-literature

Comparative analysis of cancer genes in the human and chimpanzee genomes.

Project description:BackgroundCancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes.ResultsThis analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene.ConclusionThese data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.

| S-EPMC1382208 | biostudies-literature

Chimpanzee histology and functional brain imaging show that the paracingulate sulcus is not human-specific.

Project description:The paracingulate sulcus -PCGS- has been considered for a long time to be specific to the human brain. Its presence/absence has been discussed in relation to interindividual variability of personality traits and cognitive abilities. Recently, a putative PCGS has been observed in chimpanzee brains. To demonstrate that this newly discovered sulcus is the homologue of the PCGS in the human brain, we analyzed cytoarchitectonic and resting-state functional magnetic resonance imaging data in chimpanzee brains which did or did not display a PCGS. The results show that the organization of the mid-cingulate cortex of the chimpanzee brain is comparable to that of the human brain, both cytoarchitectonically and in terms of functional connectivity with the lateral frontal cortex. These results demonstrate that the PCGS is not human-specific but is a shared feature of the primate brain since at least the last common ancestor to humans and great apes ~6 mya.

| S-EPMC7794552 | biostudies-literature

Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies.

Project description:With a draft genome-sequence assembly for the chimpanzee available, it is now possible to perform genome-wide analyses to identify, at a submicroscopic level, structural rearrangements that have occurred between chimpanzees and humans. The goal of this study was to investigate chromosomal regions that are inverted between the chimpanzee and human genomes. Using the net alignments for the builds of the human and chimpanzee genome assemblies, we identified a total of 1,576 putative regions of inverted orientation, covering more than 154 mega-bases of DNA. The DNA segments are distributed throughout the genome and range from 23 base pairs to 62 mega-bases in length. For the 66 inversions more than 25 kilobases (kb) in length, 75% were flanked on one or both sides by (often unrelated) segmental duplications. Using PCR and fluorescence in situ hybridization we experimentally validated 23 of 27 (85%) semi-randomly chosen regions; the largest novel inversion confirmed was 4.3 mega-bases at human Chromosome 7p14. Gorilla was used as an out-group to assign ancestral status to the variants. All experimentally validated inversion regions were then assayed against a panel of human samples and three of the 23 (13%) regions were found to be polymorphic in the human genome. These polymorphic inversions include 730 kb (at 7p22), 13 kb (at 7q11), and 1 kb (at 16q24) fragments with a 5%, 30%, and 48% minor allele frequency, respectively. Our results suggest that inversions are an important source of variation in primate genome evolution. The finding of at least three novel inversion polymorphisms in humans indicates this type of structural variation may be a more common feature of our genome than previously realized.

| S-EPMC1270012 | biostudies-literature

Transcriptome analysis of human and chimpanzee iPS cells

Project description:mRNA-seq were conducted for iPS cells of human-1 (409-B2/HPS0076), human-2 (Nips-B2/HPS0223), chimpanzee-1 (kiku/0138F-1), and chimpanzee-2 (mari/0274F-2). To compare gene expression levels, the reads were first mapped to the chimpanzee genome (panTro5), and mapped reads were then mapped to the human genome (hg38). Gene expression was anlyzed based on the hg38 annotation.

2022-10-26 | GSE201296 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data