scholarly journals Molecular shifts in limb identity underlie development of feathered feet in two domestic avian species

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Eric T Domyan ◽  
Zev Kronenberg ◽  
Carlos R Infante ◽  
Anna I Vickrey ◽  
Sydney A Stringham ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Single Species ◽  
Specific Transcription Factor ◽  
Regulatory Changes ◽  
Genes Encoding ◽  
Domestic Pigeons ◽  
Phenotypic Convergence

Birds display remarkable diversity in the distribution and morphology of scales and feathers on their feet, yet the genetic and developmental mechanisms governing this diversity remain unknown. Domestic pigeons have striking variation in foot feathering within a single species, providing a tractable model to investigate the molecular basis of skin appendage differences. We found that feathered feet in pigeons result from a partial transformation from hindlimb to forelimb identity mediated by cis-regulatory changes in the genes encoding the hindlimb-specific transcription factor Pitx1 and forelimb-specific transcription factor Tbx5. We also found that ectopic expression of Tbx5 is associated with foot feathers in chickens, suggesting similar molecular pathways underlie phenotypic convergence between these two species. These results show how changes in expression of regional patterning genes can generate localized changes in organ fate and morphology, and provide viable molecular mechanisms for diversity in hindlimb scale and feather distribution.

Ectopic expression of a R2R3 MYB transcription factor of dove tree (Davidia involucrata) aggravates seed abortion in Arabidopsis thaliana

2020 ◽  
Vol 47 (5) ◽  
pp. 454
Author(s):  
Jian Li ◽  
Tian Chen ◽  
Fengzhen Huang ◽  
Penghui Dai ◽  
Fuxiang Cao ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transgenic Plants ◽  
Ectopic Expression ◽  
Myb Transcription Factor ◽  
Seed Abortion ◽  
Transgenic Seeds ◽  
Genes Encoding ◽  
Colour Changes ◽  
R2r3 Myb

Serious seed abortion of dove tree (Davidia involucrate Baill.) is one of the critical factors leading to the low fecundity of this species. Seed abortion is a complicated process and various factors have been verified to synergistically determine the fate of seeds. To reveal the mechanism of seed abortion in D. involucrata, we performed transcriptome analysis in normal and abortive seeds of D. involucrata. According to the transcriptome data, we noticed that most of the genes encoding a MYB transcription factor were predominantly expressed in abortive seeds. Among these, a gene named DiMYB1 was selected and its function was validated in this study. Overexpression of DiMYB1 resulted in obviously reduced viability of transgenic seeds and seedlings, and caused a significantly higher seed abortion rate. The vegetative growth of transgenic plants was hindered, resulting in an earlier flowering time. In addition, colour changes occurred in transgenic plants. Some transgenic sprouts, stems and pods appeared purple instead of green in colour. Our finding demonstrated that DiMYB1 participates in multiple plant developmental processes, especially in seed development in Arabidopsis thaliana (L.) Heynh., which indicated the similar role of this gene in D. involucrata.

scholarly journals Multiple layers of transcriptional regulation by PLZF in NKT-cell development

2016 ◽  
Vol 113 (27) ◽  
pp. 7602-7607 ◽  
Author(s):  
Ai-Ping Mao ◽  
Michael G. Constantinides ◽  
Rebecca Mathew ◽  
Zhixiang Zuo ◽  
Xiaoting Chen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Molecular Mechanisms ◽  
Promyelocytic Leukemia ◽  
Transcriptional Program ◽  
T Helper ◽  
Nkt Cell ◽  
Btb Domain ◽  
Transcription Factor Genes ◽  
Genes Encoding

The transcription factor PLZF [promyelocytic leukemia zinc finger, encoded by zinc finger BTB domain containing 16 (Zbtb16)] is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T-helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both natural killer T (NKT) cells and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. First, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T-helper–specific transcription factor genes that in turn control T-helper–specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the multilayered architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.

scholarly journals The MYB36 transcription factor orchestrates Casparian strip formation

2015 ◽  
Vol 112 (33) ◽  
pp. 10533-10538 ◽  
Author(s):  
Takehiro Kamiya ◽  
Monica Borghi ◽  
Peng Wang ◽  
John M. C. Danku ◽  
Lothar Kalmbach ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Ectopic Expression ◽  
Casparian Strip ◽  
Strip Domain ◽  
Genes Encoding ◽  
Casparian Strips ◽  
Endodermal Cells ◽  
Respiratory Burst Oxidase ◽  
Strip Formation

The endodermis in roots acts as a selectivity filter for nutrient and water transport essential for growth and development. This selectivity is enabled by the formation of lignin-based Casparian strips. Casparian strip formation is initiated by the localization of the Casparian strip domain proteins (CASPs) in the plasma membrane, at the site where the Casparian strip will form. Localized CASPs recruit Peroxidase 64 (PER64), a Respiratory Burst Oxidase Homolog F, and Enhanced Suberin 1 (ESB1), a dirigent-like protein, to assemble the lignin polymerization machinery. However, the factors that control both expression of the genes encoding this biosynthetic machinery and its localization to the Casparian strip formation site remain unknown. Here, we identify the transcription factor, MYB36, essential for Casparian strip formation. MYB36 directly and positively regulates the expression of the Casparian strip genes CASP1, PER64, and ESB1. Casparian strips are absent in plants lacking a functional MYB36 and are replaced by ectopic lignin-like material in the corners of endodermal cells. The barrier function of Casparian strips in these plants is also disrupted. Significantly, ectopic expression of MYB36 in the cortex is sufficient to reprogram these cells to start expressing CASP1–GFP, correctly localize the CASP1–GFP protein to form a Casparian strip domain, and deposit a Casparian strip-like structure in the cell wall at this location. These results demonstrate that MYB36 is controlling expression of the machinery required to locally polymerize lignin in a fine band in the cell wall for the formation of the Casparian strip.

scholarly journals Mutations Upstream of the TBX5 and PITX1 Transcription Factor Genes Are Associated with Feathered Legs in the Domestic Chicken

2020 ◽  
Vol 37 (9) ◽  
pp. 2477-2486 ◽  
Author(s):  
Jingyi Li ◽  
MiOk Lee ◽  
Brian W Davis ◽  
Sangeet Lamichhaney ◽  
Ben J Dorshorst ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Sequence Data ◽  
Ectopic Expression ◽  
Base Change ◽  
Whole Genome Sequence ◽  
Chromosome 15 ◽  
Specific Transcription Factor ◽  
Proposed Model ◽  
Transcription Factor Genes ◽  
Causal Variants

Abstract Feathered leg is a trait in domestic chickens that has undergone intense selection by fancy breeders. Previous studies have shown that two major loci controlling feathered leg are located on chromosomes 13 and 15. Here, we present genetic evidence for the identification of candidate causal mutations at these loci. This was accomplished by combining classical linkage mapping using an experimental cross segregating for feathered leg and high-resolution identical-by-descent mapping using whole-genome sequence data from 167 samples of chicken with or without feathered legs. The first predicted causal mutation is a single-base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The second is a 17.7-kb deletion located ∼200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. The study reveals a remarkable convergence in the evolution of the feathered-leg phenotype in domestic chickens and domestic pigeons, as this phenotype is caused by noncoding mutations upstream of the same two genes. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons. The results of the present study are consistent with the previously proposed model for pigeon that feathered leg is caused by reduced PITX1 expression and ectopic expression of TBX5 in hindlimb buds resulting in a shift of limb identity from hindlimb to more forelimb-like identity.

scholarly journals Transcription Factor HMG Box-Containing Protein 1 (HBP1) Regulates Glycemic Homeostasis Through Modulation of Gluconeogenesis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1247-1247
Author(s):  
Chin-Ming Chang ◽  
Chun-Yin Huang
Keyword(s):  
Transcription Factor ◽  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Tolerance Test ◽  
Public Health Issue ◽  
Oral Glucose ◽  
Hmg Box ◽  
Blood Glucose Homeostasis

Abstract Objectives Glycemic dysregulation is one of the major metabolic disorders, which has long been a significant public health issue. The liver plays a pivotal role in the maintenance of blood glucose homeostasis. Previous studies indicate that upon refeeding a high carbohydrate diet, the expression of transcription factor HMG box-containing protein 1 (HBP1) was elevated in mice livers, suggesting a role of HBP1 in carbohydrate metabolism. Therefore, the objective of the current study was to understand the molecular mechanisms through which HBP1 regulates glucose generation in the liver. Methods Both in vivo HBP1 knockdown mice and in vitro HepG2 cell line were employed as the experimental models. Results First, we observed that overnight fasting led to increased PEPCK but decreased HBP1 expression in mice livers, and subsequent addition of insulin reversed the expression pattern. More importantly, HBP1 knockout (KO) mice displayed a significantly higher blood glucose level (173 mg/dL) than that of the controls (98 mg/dL). Also, HBP1 KO led to impaired OGTT (oral glucose tolerance test) and ITT (insulin tolerance test). These data suggest that HBP1 might have a role in the regulation of gluconeogenesis in the liver. To unveil the molecular mechanism by which HBP1 regulates glucose homeostasis, we examined its role in gluconeogenesis. Administration of gluconeogenic stimulators glucagon (100 nM) and cAMP (0.5 ng/mL) resulted in increased expression of Phosphoenolpyruvate carboxykinase (PEPCK; encoded by the PCK1 gene), a key enzyme in gluconeogenesis, but decreased HBP1 expression in HepG2 cells. Last, HBP1 siRNA-mediated mRNA disruption led to elevated PEPCK expression, whereas ectopic expression of HBP1 (pcDNA3-HBP1-Flag) significantly suppressed it. Conclusions In conclusion, our data indicate that HBP1 might negatively regulate glucose production and support HBP1 as a novel biological regulator of blood glucose homeostasis. Funding Sources This work was supported by the grant to MOST 108–2320-B-039–051-MY3 C-Y Huang.

scholarly journals Human gastrin-releasing peptide receptor gene regulation requires transcription factor binding at two distinct CRE sites

2008 ◽  
Vol 295 (1) ◽  
pp. G153-G162 ◽  
Author(s):  
Dharmaraj Chinnappan ◽  
Xiangping Qu ◽  
Dongmei Xiao ◽  
Anita Ratnasari ◽  
H. Christian Weber
Keyword(s):  
Transcription Factor ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Gastrointestinal Cancer ◽  
Molecular Mechanisms ◽  
Receptor Gene ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Wild Type ◽  
Gastrin Releasing Peptide

Ectopic expression of the gastrin-releasing peptide (GRP) receptor (GRP-R) occurs frequently in human malignancies of the gastrointestinal tract. Owing to paracrine and autocrine interaction with its specific high-affinity ligand GRP, tumor cell proliferation, migration, and invasion might ensue. Here we provide the first insights regarding molecular mechanisms of GRP-R regulation in gastrointestinal cancer cells. We identified by EMSA and chromatin immunoprecipitation assays two cAMP response element (CRE) binding sites that recruited transcription factor CRE binding protein (CREB) to the human GRP-R promoter. Transfection studies with a wild-type human GRP-R promoter reporter and corresponding CRE mutants showed that both CRE sites are critical for basal transcriptional activation in gastrointestinal cancer cells. Forced expression of cAMP-dependent effectors CREB and PKA resulted in robust upregulation of human GRP-R transcriptional activity, and this overexpression strictly required intact wild-type CRE sites. Direct cAMP stimulation with forskolin resulted in enhanced human GRP-R promoter activity only in HuTu-80 cells, but not in Caco-2 cells, coinciding with forskolin-induced CREB phosphorylation occurring only in HuTu-80 but not Caco-2 cells. In summary, CREB is a critical regulator of human GRP-R expression in gastrointestinal cancer and might be activated through different upstream intracellular pathways.

scholarly journals Landscape of allele-specific transcription factor binding in the human genome

2020 ◽  
Author(s):  
Sergey Abramov ◽  
Alexandr Boytsov ◽  
Dariia Bykova ◽  
Dmitry D. Penzar ◽  
Ivan Yevshin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Transcription Factor Binding ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Specific Transcription Factor ◽  
Factor Binding ◽  
Allele Specific

AbstractSequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.

scholarly journals Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Seiichiro Mori ◽  
Takamasa Takeuchi ◽  
Yoshiyuki Ishii ◽  
Takashi Yugawa ◽  
Tohru Kiyono ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Human Papillomavirus ◽  
Molecular Mechanisms ◽  
Cytidine Deaminase ◽  
Ectopic Expression ◽  
Human Keratinocytes ◽  
Hek293 Cells ◽  
Mrna Levels ◽  
Hpv16 E6 ◽  
Human Cancers

ABSTRACT The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers, including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites. Normal immortalized human keratinocytes expressing E6 (NIKS-E6) displayed increased levels of TEAD1/4 protein compared to parental NIKS. A series of E6 mutants revealed that E6-mediated degradation of p53 was important for increasing TEAD4 levels. Knockdown of TEADs in NIKS-E6 significantly reduced A3B mRNA levels, whereas ectopic expression of TEAD4 in NIKS increased A3B mRNA levels. Finally, chromatin immunoprecipitation assays demonstrated increased levels of TEAD4 binding to the A3B promoter in NIKS-E6 compared to NIKS. Collectively, these results indicate that E6 induces upregulation of A3B through increased levels of TEADs, highlighting the importance of the TEAD-A3B axis in carcinogenesis. IMPORTANCE The expression of APOBEC3B (A3B), a cellular DNA cytidine deaminase, is upregulated in various human cancers and leaves characteristic, signature mutations in cancer genomes, suggesting that it plays a prominent role in carcinogenesis. Viral oncoproteins encoded by human papillomavirus (HPV) and polyomavirus have been reported to induce A3B expression, implying the involvement of A3B upregulation in virus-associated carcinogenesis. However, the molecular mechanisms causing A3B upregulation remain unclear. Here, we demonstrate that exogenous expression of the cellular transcription factor TEAD activates the A3B promoter. Further, the HPV oncoprotein E6 increases the levels of endogenous TEAD1/4 protein, thereby leading to A3B upregulation. Since increased levels of TEAD4 are frequently observed in many cancers, an understanding of the direct link between TEAD and A3B upregulation is of broad oncological interest.

scholarly journals B-box transcription factor 28 regulates flowering by interacting with constans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yin Liu ◽  
Guang Lin ◽  
Chunmei Yin ◽  
Yuda Fang
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Shade Avoidance ◽  
Structural Domains ◽  
Abiotic And Biotic Stresses ◽  
Biotic Stresses ◽  
Group Members ◽  
Redundant Role

Abstract B-box transcription factors (BBXs) are important regulators of flowering, photomorphogenesis, shade-avoidance, abiotic and biotic stresses and plant hormonal pathways. In Arabidopsis, 32 BBX proteins have been identified and classified into five groups based on their structural domains. Little is known about the fifth group members (BBX26–BBX32) and the detailed molecular mechanisms relevant to their functions. Here we identified B-box transcription factor 28 (BBX28) that interacts with Constans (CO), a transcriptional activator of Flowering Locus T (FT). Overexpressing BBX28 leads to late flowering with dramatically decreased FT transcription, and bbx28 deficient mutant displays a weak early flowering phenotype under long days (LD), indicating that BBX28 plays a negative and redundant role in flowering under LD. Additionally, the interaction between BBX28 and CO decreases the recruitment of CO to FT locus without affecting the transcriptional activation activity of CO. Moreover, the N-terminal cysteines, especially those within the B-box domain, are indispensable for the heterodimerization between BBX28 and CO and activation of CO on FT transcription. Genetic evidences show that the later flowering caused by BBX28 overexpression is compromised by CO ectopic expression. Collectively, these results supported that BBX28 functions with CO and FT to negatively regulate Arabidopsis flowering, in which the N-terminal conserved cysteines of BBX28 might play a central role.

scholarly journals Hypoxic regulation of erythropoiesis and iron metabolism

2010 ◽  
Vol 299 (1) ◽  
pp. F1-F13 ◽  
Author(s):  
Volker H. Haase
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Oxygen Sensor ◽  
Hypoxia Inducible Factor ◽  
Adaptation To Hypoxia ◽  
Cellular Adaptation ◽  
Hypoxic Induction ◽  
Highly Sensitive

The kidney is a highly sensitive oxygen sensor and plays a central role in mediating the hypoxic induction of red blood cell production. Efforts to understand the molecular basis of oxygen-regulated erythropoiesis have led to the identification of erythropoietin (EPO), which is essential for normal erythropoiesis and to the purification of hypoxia-inducible factor (HIF), the transcription factor that regulates EPO synthesis and mediates cellular adaptation to hypoxia. Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review.

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