scholarly journals Conservation of the sizes of 53 introns and over 100 intronic sequences for the binding of common transcription factors in the human and mouse genes for type II procollagen (COL2A1)

1995 ◽  
Vol 308 (3) ◽  
pp. 923-929 ◽  
Author(s):  
L Ala-Kokko ◽  
A P Kvist ◽  
M Metsäranta ◽  
K I Kivirikko ◽  
B de Crombrugghe ◽  
...  

Over 11,000 bp of previously undefined sequences of the human COL2A1 gene were defined. The results made it possible to compare the intron structures of a highly complex gene from man and mouse. Surprisingly, the sizes of the 53 introns of the two genes were highly conserved with a mean difference of 13%. After alignment of the sequences, 69% of the intron sequences were identical. The introns contained consensus sequences for the binding of over 100 different transcription factors that were conserved in the introns of the two genes. The first intron of the gene contained 80 conserved consensus sequences and the remaining 52 introns of the gene contained 106 conserved sequences for the binding of transcription factors. The 5′-end of intron 2 in both genes had a potential for forming a stem loop in RNA transcripts.

1992 ◽  
Vol 285 (1) ◽  
pp. 287-294 ◽  
Author(s):  
M Vikkula ◽  
M Metsäranta ◽  
A C Syvänen ◽  
L Ala-Kokko ◽  
E Vuorio ◽  
...  

Transcription of the type-II procollagen gene (COL2A1) is very specifically restricted to a limited number of tissues, particularly cartilages. In order to identify transcription-control motifs we have sequenced the promoter region and the first intron of the human and mouse COL2A1 genes. With the assumption that these motifs should be well conserved during evolution, we have searched for potential elements important for the tissue-specific transcription of the COL2A1 gene by aligning the two sequences with each other and with the available rat type-II procollagen sequence for the promoter. With this approach we could identify specific evolutionarily well-conserved motifs in the promoter area. On the other hand, several suggested regulatory elements in the promoter region did not show evolutionary conservation. In the middle of the first intron we found a cluster of well-conserved transcription-control elements and we conclude that these conserved motifs most probably possess a significant function in the control of the tissue-specific transcription of the COL2A1 gene. We also describe locations of additional, highly conserved nucleotide stretches, which are good candidate regions in the search for binding sites of yet-uncharacterized cartilage-specific transcription regulators of the COL2A1 gene.


BMC Genomics ◽  
2020 ◽  
Vol 21 (S11) ◽  
Author(s):  
Shouguo Gao ◽  
Zhijie Wu ◽  
Xingmin Feng ◽  
Sachiko Kajigaya ◽  
Xujing Wang ◽  
...  

Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.


Spine ◽  
2001 ◽  
Vol 26 (23) ◽  
pp. 2558-2565 ◽  
Author(s):  
Janne Sahlman ◽  
Ritva Inkinen ◽  
Teemu Hirvonen ◽  
Mikko J. Lammi ◽  
Pirkko E. Lammi ◽  
...  

2005 ◽  
Vol 35 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Valérie Baldacchino ◽  
Sylvie Oble ◽  
Patrick-Olivier Décarie ◽  
Isabelle Bourdeau ◽  
Pavel Hamet ◽  
...  

The best characterized effect of glucose-dependent insulinotropic polypeptide (GIP) is its stimulatory effect on insulin secretion by pancreatic β-cells. Recently, it was demonstrated that some cases of primary adrenal Cushing’s syndrome were secondary to the ectopic expression of non-mutated GIP receptor (GIP-R) in bilateral adrenal hyperplasias or unilateral adrenal adenomas, resulting in food-dependent steroidogenesis. Using a human multiple-expression tissue array, GIP-R was found to be expressed in a large number of human adult and fetal tissues, but not in the adrenal gland. The analysis of the promoter region of human (h) GIP-R gene revealed six consensus sequences important in regulating the reporter gene activity and capable of binding to Sp1 and Sp3 transcription factors. Data obtained by gene array and semi-quantitative RT-PCR showed an increase in the expression of Sp3 and CRSP9 (co-regulator of Sp1 transcription factor, subunit 9) in the adrenal adenomas or bilateral macronodular hyperplasias of patients with GIP-dependent Cushing’s syndrome; they were, however, also increased in some patients with non-GIP-dependent cortisol-secreting adenomas or with ACTH-dependent Cushing’s disease. This study represents the first step in our understanding of the mechanisms involved in the regulation of the expression of the hGIP-R gene.


1991 ◽  
Vol 11 (5) ◽  
pp. 2832-2841
Author(s):  
N Mechti ◽  
M Piechaczyk ◽  
J M Blanchard ◽  
P Jeanteur ◽  
B Lebleu

A strong block to the elongation of nascent RNA transcripts by RNA polymerase II occurs in the 5' part of the mammalian c-fos proto-oncogene. In addition to the control of initiation, this mechanism contributes to transcriptional regulation of the gene. In vitro transcription experiments using nuclear extracts and purified transcription templates allowed us to map a unique arrest site within the mouse first intron 385 nucleotides downstream from the promoter. This position is in keeping with that estimated from nuclear run-on assays performed with short DNA probes and thus suggests that it corresponds to the actual block in vivo. Moreover, we have shown that neither the c-fos promoter nor upstream sequences are absolute requirements for an efficient transcription arrest both in vivo and in vitro. Finally, we have characterized a 103-nucleotide-long intron 1 motif comprising the arrest site and sufficient for obtaining the block in a cell-free transcription assay.


1988 ◽  
Vol 8 (5) ◽  
pp. 2042-2051
Author(s):  
K Wiebauer ◽  
J J Herrero ◽  
W Filipowicz

The report that human growth hormone pre-mRNA is not processed in transgenic plant tissues (A. Barta, K. Sommergruber, D. Thompson, K. Hartmuth, M.A. Matzke, and A.J.M. Matzke, Plant Mol. Biol. 6:347-357, 1986) has suggested that differences in mRNA splicing processes exist between plants and animals. To gain more information about the specificity of plant pre-mRNA processing, we have compared the splicing of the soybean leghemoglobin pre-mRNA with that of the human beta-globin pre-mRNA in transfected plant (Orychophragmus violaceus and Nicotiana tabacum) protoplasts and mammalian (HeLa) cells. Of the three introns of leghemoglobin pre-mRNA, only intron 2 was correctly and efficiently processed in HeLa cells. The 5' splice sites of the remaining two introns were faithfully recognized, but correct processing of the 3' sites took place only rarely (intron 1) or not at all (intron 3); cryptic 3' splice sites were used instead. While the first intron in human beta-globin pre-mRNA was not spliced in transfected plant protoplasts, intron 2 processing occurred at a low level, indicating that some mammalian introns can be recognized by the plant intron-splicing machinery. However, excision of intron 2 proved to be incorrect, involving the authentic 5' splice site and a cryptic 3' splice site. Our results indicate that the mechanism of 3'-splice-site selection during intron excision differs between plants and animals. This conclusion is supported by analysis of the 3'-splice-site consensus sequences in animal and plant introns which revealed that polypyrimidine tracts, characteristic of animal introns, are not present in plant pre-mRNAs. It is proposed that an elevated AU content of plant introns is important for their processing.


2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
David Talavera ◽  
Modesto Orozco ◽  
Xavier de la Cruz

Functional modification of transcription regulators may lead to developmental changes and phenotypical differences between species. In this work, we study the influence of alternative splicing on transcription factors in human and mouse. Our results show that the impact of alternative splicing on transcription factors is similar in both species, meaning that the ways to increase variability should also be similar. However, when looking at the expression patterns of transcription factors, we observe that they tend to diverge regardless of the role of alternative splicing. Finally, we hypothesise that transcription regulation of alternatively spliced transcription factors could play an important role in the phenotypical differences between species, without discarding other phenomena or functional families.


1994 ◽  
Vol 158 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Douglass M. Bradham ◽  
Beatrix In Der Wiesche ◽  
Patricia Precht ◽  
Richard Balakir ◽  
Walter Horton

2005 ◽  
Vol 03 (04) ◽  
pp. 949-964 ◽  
Author(s):  
RONGXIANG LIU ◽  
PANKAJ AGARWAL

The response of genes to cell stimuli is often measured by microarrays. However, studying the function of these genes rarely elucidate as to how the stimuli activate or suppress these genes. To understand the mechanisms of cell stimulation, we describe a computational method for analyzing mammalian promoters of early response genes to detect the transcription factors activated by cell stimulation. We first analyzed promoters of the response genes, for transcription factor binding sites conserved between human and mouse. We then applied hypergeometric statistics in conjunction with Bonferroni correction to identify the top transcription factors whose binding sites were significantly over-represented among these promoters. In five data sets with early response genes, a significantly larger than expected number of genes had binding sites in their promoters for transcription factors previously known to be involved in response to the stimulus, while data sets with measurements at longer time points (24 hours) failed to show such over-representation. Because the end points of signal transduction pathways are transcription factors, this methodology is useful for exploring signaling pathways activated by various stimuli through microarray studies.


2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.


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