scholarly journals Evolutionary footprints reveal insights into plant microRNA biogenesis

2017 ◽  
Author(s):  
Uciel Chorostecki ◽  
Belen Moro ◽  
Arantxa M.L. Rojas ◽  
Juan M. Debernardi ◽  
Arnaldo L. Schapire ◽  
...  
Keyword(s):  
Binding Sites ◽  
Small Rnas ◽  
Target Genes ◽  
Graphical Representation ◽  
Mirna Biogenesis ◽  
Plant Mirnas ◽  
Structural Determinants ◽  
Plant Mirna ◽  
Conservation Patterns

AbstractMicroRNAs (miRNAs) are endogenous small RNAs that recognize target sequences by base complementarity. They are processed from longer precursors that harbor a fold-back structure. Plant miRNA precursors are quite variable in size and shape, and are recognized by the processing machinery in different ways. However, ancient miRNAs and their binding sites in target genes are conserved during evolution. Here, we designed a strategy to systematically analyze MIRNAs from different species generating a graphical representation of the conservation of the primary sequence and secondary structure. We found that plant MIRNAs have evolutionary footprints that go beyond the small RNA sequence itself, yet, their location along the precursor depends on the specific MIRNA. We show that these conserved regions correspond to structural determinants recognized during the biogenesis of plant miRNAs. Furthermore, we found that the members of the miR166 family have unusual conservation patterns and demonstrated that the recognition of these precursors in vivo differs from other known miRNAs. Our results describe a link between the evolutionary conservation of plant MIRNAs and the mechanisms underlying the biogenesis of these small RNAs, and show that the MIRNA pattern of conservation can be used to infer the mode of miRNA biogenesis.

MicroRNA annotation in plants: current status and challenges

2021 ◽  
Author(s):  
Yongxin Zhao ◽  
Zheng Kuang ◽  
Ying Wang ◽  
Lei Li ◽  
Xiaozeng Yang
Keyword(s):  
Small Rna ◽  
Signal To Noise Ratio ◽  
Current Status ◽  
Mirna Biogenesis ◽  
Plant Mirnas ◽  
Signal To Noise ◽  
Advantages And Disadvantages ◽  
Plant Mirna ◽  
History Of ◽  
Mirna Biogenesis Pathway

Abstract Last two decades, the studies on microRNAs (miRNAs) and the numbers of annotated miRNAs in plants and animals have surged. Herein, we reviewed the current progress and challenges of miRNA annotation in plants. Via the comparison of plant and animal miRNAs, we pinpointed out the difficulties on plant miRNA annotation and proposed potential solutions. In terms of recalling the history of methods and criteria in plant miRNA annotation, we detailed how the major progresses made and evolved. By collecting and categorizing bioinformatics tools for plant miRNA annotation, we surveyed their advantages and disadvantages, especially for ones with the principle of mimicking the miRNA biogenesis pathway by parsing deeply sequenced small RNA (sRNA) libraries. In addition, we summarized all available databases hosting plant miRNAs, and posted the potential optimization solutions such as how to increase the signal-to-noise ratio (SNR) in these databases. Finally, we discussed the challenges and perspectives of plant miRNA annotations, and indicated the possibilities offered by an all-in-one tool and platform according to the integration of artificial intelligence.

scholarly journals Cross-Kingdom Regulation by Plant microRNAs Provides Novel Insight into Gene Regulation

2020 ◽  
Author(s):  
Abdul Fatah A Samad ◽  
Mohd Farizal Kamaroddin ◽  
Muhammad Sajad
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Current Knowledge ◽  
Circulatory System ◽  
Dietary Therapy ◽  
Transcriptional Level ◽  
Plant Mirnas ◽  
Health Issues ◽  
Plant Mirna ◽  
Potential Applications

ABSTRACT microRNAs (miRNAs) are well known as major players in mammalian and plant genetic systems that act by regulating gene expression at the post-transcriptional level. These tiny molecules can regulate target genes (mRNAs) through either cleavage or translational inhibition. Recently, the discovery of plant-derived miRNAs showing cross-kingdom abilities to regulate mammalian gene expression has prompted exciting discussions among researchers. After being acquired orally through the diet, plant miRNAs can survive in the digestive tract, enter the circulatory system, and regulate endogenous mRNAs. Here, we review current knowledge regarding the cross-kingdom mechanisms of plant miRNAs, related controversies, and potential applications of these miRNAs in dietary therapy, which will provide new insights for plant miRNA investigations related to health issues in humans.

scholarly journals The TEA Transcription Factor Tec1 Confers Promoter-Specific Gene Regulation by Ste12-Dependent and -Independent Mechanisms

2010 ◽  
Vol 9 (4) ◽  
pp. 514-531 ◽  
Author(s):  
Barbara Heise ◽  
Julia van der Felden ◽  
Sandra Kern ◽  
Mario Malcher ◽  
Stefan Brückner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Specific Gene ◽  
Dependent Manner ◽  
A Genome ◽  
Regulated Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.

C/ebpα and Pu.1 Are Members of a Critical Regulatory Network Required for Hoxa9-Mediated Immortalization

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 650-650
Author(s):  
Cailin Collins ◽  
Jingya Wang ◽  
Joel Bronstein ◽  
Jay L. Hess
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Target Genes ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Epigenetic Modifications ◽  
Conditional Knockout ◽  
Motif Analysis ◽  
Myeloid Leukemias

Abstract Abstract 650 HOXA9 is a homeodomain-containing transcription factor that plays important roles in both development and hematopoiesis. Deregulation of HOXA9 occurs in a variety of acute lymphoid and myeloid leukemias and plays a key role in their pathogenesis. More than 50% of acute myeloid leukemia (AML) cases show up-regulation of HOXA9, which correlates strongly with poor prognosis. Nearly all cases of AML with mixed lineage leukemia (MLL) translocations have increased HOXA9 expression, as well as cases with mutation of the nucleophosmin gene NPM1, overexpression of CDX2, and fusions of NUP98. Despite the crucial role that HOXA9 plays in development, hematopoiesis and leukemia, its transcriptional targets and mechanisms of action are poorly understood. Previously we identified Hoxa9 and Meis1 binding sites in myeloblastic cells, profiled their epigenetic modifications, and identified the target genes regulated by Hoxa9. Hoxa9 and Meis1 co-bind at hundreds of promoter distal, highly evolutionarily conserved sites showing high levels of histone H3K4 monomethylation and CBP/p300 binding characteristic of enhancers. Hoxa9 association at these sites correlates strongly with increases in histone H3K27 acetylation and activation of downstream target genes, including many proleukemic gene loci. De novo motif analysis of Hoxa9 binding sites shows a marked enrichment of motifs for the transcription factors in the C/EBP and ETS families, and C/ebpα and the ETS transcription factor Pu.1 were found to cobind at Hoxa9-regulated enhancers. Both C/ebpα and Pu.1 are known to play critical roles in the establishment of functional enhancers during normal myeloid development and are mutated or otherwise deregulated in various myeloid leukemias. To determine the importance of co-association of Hoxa9, C/ebpα and Pu.1 at myeloid enhancers, we generated cell lines from C/ebpα and Pu.1 conditional knockout mice (kindly provided by Dr. Daniel Tenen, Harvard University) by immortalization with Hoxa9 and Meis1. In addition we transformed bone marrow with a tamoxifen-regulated form of Hoxa9. Strikingly, loss of C/ebpα or Pu.1, or inactivation of Hoxa9, blocks proliferation and leads to myeloid differentiation. ChIP experiments show that both C/ebpα and Pu.1 remain bound to Hoxa9 binding sites in the absence of Hoxa9. After the loss of Pu.1, both Hoxa9 and C/ebpα dissociate from Hoxa9 binding sites with a corresponding decrease in target gene expression. In contrast, loss of C/ebpα does not lead to an immediate decrease in either Hoxa9 or Pu.1 binding, suggesting that C/ebpα may be playing a regulatory as opposed to a scaffolding role at enhancers. Current work focuses on performing ChIP-seq analysis to assess how C/ebpα and Pu.1 affect Hoxa9 and Meis1 binding and epigenetic modifications genome-wide, and in vivo leukemogenesis assays to confirm the requirement of both Pu.1 and C/ebpα in the establishment and maintenance of leukemias with high levels of Hoxa9. Collectively, our findings implicate C/ebpα and Pu.1 as members of a critical transcription factor network required for Hoxa9-mediated transcriptional regulation in leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Novel Mechanism of Positive versus Negative Regulation by Thyroid Hormone Receptor β1 (TRβ1) Identified by Genome-wide Profiling of Binding Sites in Mouse Liver

2013 ◽  
Vol 289 (3) ◽  
pp. 1313-1328 ◽  
Author(s):  
Preeti Ramadoss ◽  
Brian J. Abraham ◽  
Linus Tsai ◽  
Yiming Zhou ◽  
Ricardo H. Costa-e-Sousa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Thyroid Hormone ◽  
Binding Sites ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Negative Regulation ◽  
Genome Wide

Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TRβ1. However, the number of known target genes directly regulated by TRβ1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TRβ1 cistrome in vivo, we expressed a biotinylated TRβ1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRβ1 targets, and correlated these data with gene expression changes. As with other nuclear receptors, the majority of TRβ1 binding sites were not in proximal promoters but in the gene body of known genes. Remarkably, T3 can dictate changes in TRβ1 binding, with strong correlation to T3-induced gene expression changes, suggesting that differential TRβ1 binding regulates transcriptional outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at binding sites where T3 induced an increase or decrease in TRβ1 binding, respectively, leading to either positive or negative regulation by T3. Taken together, the results of this study provide new insights into the mechanisms of transcriptional regulation by TRβ1 in vivo.

scholarly journals Identification of in vivo Hox13 binding sites reveals an essential locus controlling zebrafish brachyury expression

Development ◽  
2021 ◽  
Author(s):  
Zhi Ye ◽  
Christopher R. Braden ◽  
Andrea Wills ◽  
David Kimelman
Keyword(s):  
Binding Sites ◽  
Target Genes ◽  
Early Embryogenesis ◽  
Axis Formation ◽  
Direct Connection ◽  
Start Site ◽  
Transcription Start ◽  
Vertebrate Embryo ◽  
Response Site

During early embryogenesis the vertebrate embryo extends from anterior to posterior due to the progressive addition of cells from a posteriorly localized neuromesodermal progenitor (NMp) population. An autoregulatory loop between Wnt and Brachyury/Tbxt is required for the NMps to retain mesodermal potential, and hence normal axis development. We recently showed that the Hox13 genes help to support body axis formation and to maintain the autoregulatory loop, although the direct Hox13 target genes were unknown. Here, using a new method for identifying in vivo transcription factor binding sites, we identified over 500 potential Hox13 targets. Importantly, we found two highly conserved Hox13 binding elements far from the tbxta transcription start site, which also contain a conserved Tcf7/Lef1 (Wnt response) site. We show that the proximal of the two elements is sufficient to confer somitogenesis stage expression to a tbxta promoter that alone only drives NMp expression during gastrulation. Importantly, elimination of this proximal element produces shortened embryos due to aberrant formation of the most posterior somites. Our study provides a potential direct connection between Hox13 and regulation of the Wnt/Brachyury loop.

beta3-tubulin is directly repressed by the engrailed protein in Drosophila

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2527-2536 ◽  
Author(s):  
N. Serrano ◽  
H.W. Brock ◽  
F. Maschat
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Transgenic Line ◽  
Target Genes ◽  
Regulatory Protein ◽  
Polytene Chromosomes ◽  
First Intron ◽  
Direct Target

In Drosophila, Engrailed is a nuclear regulatory protein with essential roles during embryonic development. Although Engrailed is a transcription factor, little progress has been achieved in identifying its target genes. We report here the identification of an effector gene, the beta3-tubulin gene, as a direct target of Engrailed. The cytological location of beta3-tubulin, 60C, is a strong site of Engrailed binding on polytene chromosomes. Immunostaining analysis of a transgenic line containing a P[beta3-tubulin-lacZ] construct shows an additional site of Engrailed binding at the location of the transgene. Molecular analysis allowed identification of several Engrailed binding sites, both in vitro and in vivo, within the first intron of the beta3-tubulin locus. Engrailed binding sites identified in vitro are active in larvae. Furthermore, expression of beta3-tubulin is derepressed in the ectoderm of engrailed mutant embryos. Repression of beta3-tubulin by Engrailed is also obtained when Engrailed is ectopically expressed in embryonic mesoderm. Finally, two different sets of Engrailed binding sites are shown to be involved in the early and late regulation of beta3-tubulin by Engrailed during embryogenesis.

Specific DNA recognition and intersite spacing are critical for action of the bicoid morphogen

1994 ◽  
Vol 14 (5) ◽  
pp. 3364-3375
Author(s):  
S D Hanes ◽  
G Riddihough ◽  
D Ish-Horowicz ◽  
R Brent
Keyword(s):  
Amino Acid ◽  
Pattern Formation ◽  
Binding Sites ◽  
Target Genes ◽  
Alpha Helix ◽  
Crystallographic Analysis ◽  
Yeast Cells ◽  
Dna Specificity ◽  
Drosophila Embryos

We examined DNA site recognition by Bicoid and its importance for pattern formation in developing Drosophila embryos. Using altered DNA specificity Bicoid mutants and appropriate reporter genes, we show that Bicoid distinguishes among related DNA-binding sites in vivo by a specific contact between amino acid 9 of its recognition alpha-helix (lysine 50 of the homeodomain) and bp 7 of the site. This result is consistent with our earlier results using Saccharomyces cerevisiae but differs from that predicted by crystallographic analysis of another homeodomain-DNA interaction. Our results also demonstrate that Bicoid binds directly to those genes whose transcription it regulates and that the amino acid 9 contact is necessary for Bicoid to direct anterior pattern formation. In both Drosophila embryos and yeast cells, Bicoid requires multiple binding sites to activate transcription of target genes. We find that the distance between binding sites is critical for Bicoid activation but that, unexpectedly, this critical distance differs between Drosophila and S. cerevisiae. This result suggests that Bicoid activation in Drosophila might require an ancillary protein(s) not present in S. cerevisiae.

scholarly journals Genome-Wide Pattern of TCF7L2/TCF4 Chromatin Occupancy in Colorectal Cancer Cells

2008 ◽  
Vol 28 (8) ◽  
pp. 2732-2744 ◽  
Author(s):  
Pantelis Hatzis ◽  
Laurens G. van der Flier ◽  
Marc A. van Driel ◽  
Victor Guryev ◽  
Fiona Nielsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Binding Sites ◽  
Motif Discovery ◽  
Target Genes ◽  
Expression Profiles ◽  
Cancer Cell Line ◽  
Colorectal Cancer Cell Line ◽  
Genome Wide

ABSTRACT Wnt signaling activates gene expression through the induced formation of complexes between DNA-binding T-cell factors (TCFs) and the transcriptional coactivator β-catenin. In colorectal cancer, activating Wnt pathway mutations transform epithelial cells through the inappropriate activation of a TCF7L2/TCF4 target gene program. Through a DNA array-based genome-wide analysis of TCF4 chromatin occupancy, we have identified 6,868 high-confidence TCF4-binding sites in the LS174T colorectal cancer cell line. Most TCF4-binding sites are located at large distances from transcription start sites, while target genes are frequently “decorated” by multiple binding sites. Motif discovery algorithms define the in vivo-occupied TCF4-binding site as evolutionarily conserved A-C/G-A/T-T-C-A-A-A-G motifs. The TCF4-binding regions significantly correlate with Wnt-responsive gene expression profiles derived from primary human adenomas and often behave as β-catenin/TCF4-dependent enhancers in transient reporter assays.

Characterization of the LacI-type transcriptional repressor RbsR controlling ribose transport in Corynebacterium glutamicum ATCC 13032

Microbiology ◽  
2009 ◽  
Vol 155 (1) ◽  
pp. 150-164 ◽  
Author(s):  
Svenja S. Nentwich ◽  
Karina Brinkrolf ◽  
Lars Gaigalat ◽  
Andrea T. Hüser ◽  
Daniel A. Rey ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Binding Sites ◽  
Target Genes ◽  
Regulatory Gene ◽  
Mrna Level ◽  
Regulatory Protein ◽  
Mobility Shift ◽  
Transcriptional Induction

The gene products of the rbsRACBD (rbs) operon of C. glutamicum (cg1410–cg1414) encode a ribose-specific ATP-binding cassette (ABC) transport system and its corresponding regulatory protein (RbsR). Deletion of the structural genes rbsACBD prohibited ribose uptake. Deletion of the regulatory gene rbsR resulted in an increased mRNA level of the whole operon. Analysis of the promoter region of the rbs operon by electrophoretic mobility shift assays identified a catabolite-responsive element (cre)-like sequence as the RbsR-binding site. Additional RbsR-binding sites were identified in front of the recently characterized uriR operon (uriR-rbsK1-uriT-uriH) and the ribokinase gene rbsK2. In vitro, the repressor RbsR bound to its targets in the absence of an effector. A probable negative effector of RbsR in vivo is ribose 5-phosphate or a derivative thereof, since in a ribokinase (rbsK1 rbsK2) double mutant, no derepression of the rbs operon in the presence of ribose was observed. Analysis of the ribose stimulon in the C. glutamicum wild-type revealed transcriptional induction of the uriR and rbs operons as well as of the rbsK2 gene. The inconsistency between the existence of functional RbsR-binding sites upstream of the ribokinase genes, their transcriptional induction during growth on ribose, and the missing induction in the rbsR mutant suggested the involvement of a second transcriptional regulator. Simultaneous deletion of the regulatory genes rbsR and uriR finally demonstrated a transcriptional co-control of the rbs and uriR operons and the rbsK2 gene by both regulators, RbsR and UriR, which were furthermore shown to recognize the same cognate DNA sequences in the operators of their target genes.

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