Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Transcriptional regulation of endothelial dysfunction in atherosclerosis:an epigenetic perspective

Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.

Molecular Characterization, Expression Pattern and Transcriptional Regulation of Figla During Gonad Development in Japanese Founder (Paralichthys olivaceus)

The factor in the germline alpha(figla), as a member of the basic helix-loop-helix family, has been reported to be involved in ovary development in mammals and teleosts. However, the regulatory mechanisms of figla in teleosts remain unclear. Here,figla in P. olivaceus(Pofigla) was characterized with encoding a 202 amino acid protein that contains a conserved basic region and helix-loop-helix(HLH) domain. Amino acids alignment and synteny analysis revealed that Pofigla was conserved with the orthologous gene sequences in other vertebrates. The results of qRT-PCR showed Pofigla was maternally inherited during embryonic development. For tissue distribution, Pofigla showed a sexually dimorphic gene expression in the gonad of different genders, with a higher expression in ovary than in testis. In situ hybridization(ISH) results demonstrated Pofigla was specifically expressed in germ cells including oocytes, spermatogonia and spermatocytes. By screening and analyzing two proximal regions(-2966/-2126 and-772/-444) with high promoter activity, we found SOX5, LEF1, FOXP1 and GATA1 may play important roles in the transcriptional regulation of Pofigla. Furthermore, we observed the co-localization between Figla and LEF1 in HEK 293T cells. And the significant up-regulation effect of the canonical Wnt signaling pathway on the expression of Pofigla was found in cultured ovarian cells. This study provided the first evidence that figla not only has an important function in ovary development, but also plays some potential roles in testis development and/or male germ cell differentiation during early testis development in P. olivaceus. The results provide valuable reference in exploring the regulatory network of figla in teleost.

Transcription factor ZmNAC126 plays an important role in transcriptional regulation of maize starch synthesis-related genes

Maize(Zea mays L.)is one of the most important food crops in the world,and starch is the main component of its endosperm.Transcriptional regulation plays a vital role in starch biosynthesis.However,it is not well understood in maize.We report the identification of the transcription factor ZmNAC126 and its role in regulation of starch synthesis in maize.Transcriptional expression of ZmNAC126 was higher in maize endosperm and kernels than in roots or stems.ZmNAC126 shared a similar expression pattern with starch synthesis genes during seed development,and its expression pattern was also consistent with the accumulation of starch.ZmNAC126 is a typical transcription factor with a transactivation domain between positions 201 and 227 of the amino acid sequence,is located in the nucleus,and binds to CACG repeats in vitro.Yeast one-hybrid assay revealed that ZmNAC126 bound the promoters of ZmGBSSI,ZmSSIIa,ZmSSIV,ZmISA1,and ZmISA2.Transient overexpression of ZmNAC126 in maize endosperm increased the activities of promoters pZmSh2,pZmBt2,pZmGBSSI,pZmSSIIIa,and pZmBT1 but inhibited the activities of pZmISA1 and pZmISA2.ZmNAC126 thus acts in starch synthesis by transcriptionally regulating targeted starch synthesis-related genes in maize kernels.

Coordinated Transcriptional Regulation by the UVB Photoreceptor and Multiple Transcription Factors for Plant UV-B Responses

Non-damaging ultraviolet B(UV-B)light promotes photomorphogenic development and stress acclimation through UV-B-specific signal transduction in Arabidopsis.UV-B irradiation induces monomerization and nuclear translocation of the UV-B photoreceptor UV RESISTANCE LOCUS 8(UVR8).However,it is not clear how the nuclear localization of UVR8 leads to changes in global gene expression.Here,we reveal that nuclear UVR8 governs UV-B-responsive transcriptional networks in concert with several previously known transcription factors,including ELONGATED HYPOCOTYL 5(HY5)and PHYTOCHROME INTERACTING FACTOR 4(PIF4).Based on the transcriptomic analysis,we identify MYB13 as a novel positive regulator in UV-B-induced cotyledon expansion and stress acclimation.MYB13 is UV-B inducible and is predominantly expressed in the cotyledons.Our results demonstrate that MYB13 protein functions as a transcription factor to regulate the expression of genes involved in auxin response and flavonoid biosynthesis through direct binding with their promoters.In addition,photoactivated UVR8 interacts with MYB13 in a UV-B-dependent manner and differentially modulates the affinity of MYB13 with its targets.Taken together,our results elucidate the cooperative function of the UV-B photoreceptor UVR8 with various transcription factors in the nucleus to orchestrate the expression of specific sets of downstream genes and,ultimately,mediate plant responses to UV-B light.

Transcriptional Regulation of Lipid Catabolism during Seedling Establishment

Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth,but how this process is regulated is not well understood.Here,we show that an AT-hook motif-containing nuclear localized(AHL)protein regulates lipid mobilization and fatty acid p-oxidation during seed germination and seedling establishment.AHL4 was identified to directly interact with the lipid mediator phosphatidic acid(PA).Knockout(KO)of AHL4 enhanced,but overexpression(OE)of AHL4 attenuated,triacylglycerol(TAG)degradation and seedling growth.Normal seedling growth of the OE lines was restored by sucrose supplementation to the growth medium.AHL4-OE seedlings displayed decreased expression of genes involved in TAG hydrolysis and fatty acid oxidation,whereas the opposite was observed in AHL4-KOs.These genes contained AHL4-binding cis elements,and AHL4 was shown to bind to the promoter regions of genes encoding the TAG lipases SDP1 and DALL5 and acyl-thioesterase KAT5.These AHL4-DNA interactions were suppressed by PA species that bound to AHL4.These results indicate that AHL4 suppresses lipid catabolism by repressing the expression of specific genes involved in TAG hydrolysis and fatty acid oxidation,and that PA relieves AHL4-mediated suppression and promotes TAG degradation.Thus,AHL4 and PA together regulate lipid degradation during seed germination and seedling establishment.

Transcriptional Regulation of Secondary Growth and Wood Formation

Secondary growth and wood formation are products of the vascular cambium, a lateral meristem. Although the mechanisms have only recently begun to be uncovered, transcriptional regulation appears increasingly central to the regulation of secondary growth. The importance of transcriptional regulation is illustrated by the correlation of expression of specific classes of genes with related biological processes occurring at specific stages of secondary growth, including cell division, cell expansion, and cell differentiation. At the same time, transcription factors have been characterized that affect specific aspects of secondary growth, including regulation of the cambium and differentiation of cambial daughter cells. In the present review, we summarize evidence pointing to transcription as a major mechanism for regulation of secondary growth, and outline future approaches for comprehensively describing transcriptional networks underlying secondary growth.

Transcriptional Regulation and Signaling in Phosphorus Starvation: What About Legumes?

The availability of soil phosphorus （P）, an essential element, is one of the most important requirements for plant growth and crop production. The morphological and physiological adaptations evolved by plants to cope with P starvation have been well characterized. Several P deficiency plant responses are regulated at the transcriptional level. Microarray analysis has generated valuable information on global gene expression in Arabidopsis thaliana grown under P-stress. Despite the identification of P responsive genes, little is known about the regulation of gene expression changes. Four transcription factors, PHRI, WRKY75, ZAT6 and BHLH32, involved in P starvation signaling have been characterized in Arabidopsis, and signaling pathways are deciphered. This review analyzes the current knowledge of transcriptional regulation of P starvation responses in Arabidopsis vis-a-vis legumes such as lupine, common bean and Medicago truncatula. The knowledge on regulatory and signaling mechanisms involved in P acquisition and use in legumes will be useful for improvement of these crops, which account for a large proportion of the world＇s crop production, providing good nutritional quality feed and food.

Transcriptional regulation of oil biosynthesis inseed plants: Current understanding, applications,and perspectives

Plants produce and accumulate triacylglycerol(TAG)in their seeds as an energy reservoir to support the processes of seed germination and seedling development.Plant seed oils are vital not only for the human diet but also as renewable feedstocks for industrial use.TAG biosynthesis consists of two major steps:de novo fatty acid biosynthesis in the plastids and TAG assembly in the endoplasmic reticulum.The latest advances in unraveling transcriptional regulation have shed light on the molecular mechanisms of plant oil biosynthesis.We summarize recent progress in understanding the regulatory mechanisms of wellcharacterized and newly discovered transcription factors and other types of regulators that control plant fatty acid biosynthesis.The emerging picture shows that plant oil biosynthesis responds to developmental and environmental cues that stimulate a network of interacting transcriptional activators and repressors,which in turn fine-tune the spatiotemporal regulation of the pathway genes.

Transcriptional and post‑transcriptional regulation of RNAi‑related gene expression during plant‑virus interactions

As sessile organisms,plants encounter diverse invasions from pathogens including viruses.To survive and thrive,plants have evolved multilayered defense mechanisms to combat virus infection.RNAi,also known as RNA silencing,is an across-kingdom innate immunity and gene regulatory machinery.Molecular framework and crucial roles of RNAi in antiviral defense have been well-characterized.However,it is largely unknown that how RNAi is transcriptionally regulated to initiate,maintain and enhance cellular silencing under normal or stress conditions.Recently,insights into the transcriptional and post-transcriptional regulation of RNAi-related genes in different physiological processes have been emerging.In this review,we integrate these new findings to provide updated views on how plants modulate RNAi machinery at the(post-)transcriptional level to respond to virus infection.

Isolation and functional analysis of SrMYB1,a direct transcriptional repressor of SrUGT76G1 in Stevia rebaudiana

SrUGT76G1,the most well-studied diterpene glycosyltransferase in Stevia rebaudiana,is key to the biosynthesis of economically important steviol glycosides(SGs).However,the molecular regulatory mechanism of SrUGT76G1 has rarely been explored.In this study,we identified a MYB transcription factor,SrMYB1,using a yeast one-hybrid screening assay.SrMYB1 belongs to the typical R2R3-type MYB protein and is specifically localized in the nucleus with strong transactivation activity.The transcript of SrMYB1 is predominantly accumulated in flowers,but is also present at a lower level in leaves.Yeast one-hybrid and electrophoretic mobility shift assays verified that SrMYB1 binds directly to the MYB binding sites in the F4-3 fragment(+50–(–141))of the SrUGT76G1 promoter.Furthermore,we found that SrMYB1 could significantly repress the expression of SrUGT76G1 in both epidermal cells of tobacco leaves and stevia callus.Taken together,our results demonstrate that SrMYB1 is an essential upstream regulator of SrUGT76G1 and provide novel insight into the regulatory network for the SGs metabolic pathway in S.rebaudiana.

Computational Analysis of the Transcriptional Regulation of the Actin Family

Transcriptional regulation is a very important regulatory step in the regulation of gene expression. Transcription factors (TFs) play an important role in controlling the temporal special specificity of gene expression. The regulation area of actin genes was analyzed statistically to predict the transcription factor binding sites in the regulatory area. A group of transcription factors located in most of the sequences is believed to play an important role in co-regulating the expression of actin genes.

The BEL1-like transcription factor GhBLH5-A05 participates in cotton response to drought stress

Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.

A novel SATB1 binding site in the BCL2 promoter region possesses transcriptional regulatory function

BCL2 is a key regulator of apoptosis.Our previous work has demonstrated that special AT-rich sequence-binding protein 1 （SATB1） is positively correlated with BCL2 expression.In the present study,we report a new SATB1 binding site located between P1 and P2 promoters of the BCL2 gene.The candidate SATB1 binding sequence predicted by bioinformatic analysis was investigated in vitro and in vivo by electrophoretic gel mobility shift assays （EMSA） and chromatin immunoprecipitation （ChIP）.One 25-bp sequence,named SB1,was confirmed to be SATB1 binding site.The regulatory function of SB1 and its relevance to SATB1 were further examed with dual-luciferase reporter assay system in Jurkat cells.We found that SB1 could negatively regulate reporter gene activity.Mutation of SATB1 binding site further repressed the activity.Knockdown of SATB1 also enhanced this negative effect of SB1.Our data indicate that the SB1 sequence possesses negative transcriptional regulatory function and this function can be antagonized by SATB1.

SIMYB1 and SIMYB2, two new MYB genes from tomato, transcriptionally regulate cellulose biosynthesis in tobacco

Cellulose, a major constituent of plant biomass, is synthesized by a cellulose synthase complex. It has been demonstrated that MYB genes transcriptionally regulate cellulose synthase in Arabidopsis. However, little is known about this process in tomato. Here, two MYB （SIMYB1/2） and three cellulose synthase （CESA） （SICESA41516） genes were isolated. SIMYB1/2 and SICESA4/5/6 accumulation was found to correspond to cellulose accumulation in different tissues of tomato. Dual luciferase assays indicated that these two MYBs were transcriptional activators that interact with promoters of SICESA4/5/6. Moreover, SIMYB2 could also activate promoters of SIMYB1/2, suggesting the possible underlying auto-activation mech- anisms for MYB transcription factors. Transient over-expression of SlMYB1/2 in Nicotiana tabacum up-regulated tobacco endogenous NtCESA genes and increased cellulose accumulation. The function of SIMYB112 was further investigated using stable transformation and the results indicated that N. tabacum lines heterologous expressing SIMYB1/2 displayed a pleiotropic phenotype, long and narrow leaves, with NtCESA induced and significant increase of cellulose. In conclusion, our data suggest that tomato SIMYB1/2 have transcriptional regulatory roles in cellulose biosynthesis and SIMYB2 was more effective than SIMYB1, which may due to the transcriptional activation by SIMYB2 on SIMYB1 and itself.

Class Ⅱ transactivator(CIITA)mediates transcriptional repression of pdk4 gene by interacting with hypermethylated in cancer 1(HIC1)

Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key enzyme involved in fatty oxidation and energy expenditure, and its expression can be repressed by pro-inflammatory stimuli. Previously, we have shown that class II transactivator （CIITA） mediates the adverse effect of interferon gamma （IFN-7） in skeletal muscle cells by cooperating with hypermethylated in cancer 1 （HIC1） to repress silent informa- tion regulator 1 （SIRT1） transcription. Building upon this finding, we report here that CIITA interacted with HIC1 via the GTP-binding domain （GBD） while HIC1 interacted with CIITA via the BTB/POZ domain. The GBD domain was required for CIITA to repress SIRT1 transcription probably acting as a bridge for CIITA to bind to HIC1 and consequently to bind to the SIRT1 promoter. IFN-7 stimulation, CIITA over-expression, or HIC1 over- expression repressed Pdk4 promoter activity while silencing either CIITA or HIC1 normalized Pdk4 expression in the presence of IFN-7. An increase in SIRT1 expression or activity partially rescued Pdk4 expression in the pre- sence of CIITA, but SIRT1 inhibition abrogated Pdk4 normalization even in the absence of CIITA. Taken together, our data have identified a HIC1-CIITA-SIRT1 axis that regulates Pdk4 transcription in response to IFN-7 stimula- tion.

Mechanisms of MYB-bHLH-WD40 Complex in the Regulation of Anthocyanin Biosynthesis in Plants

Anthocyanins are main coloring substances in plants with various functions such as antioxidant , preventing cardiovascular diseases , and inhibiting oncogenesis. The regulation of transcriptional levels plays a decisive role in the biosynthesis of anthocyanins. Studies have shown that the transcriptional levels of an- thocyanins are mainly regulated by MYB-bHLH-WD40 ternary complex. This paper summarized the structure characteristics of MYB-bHLH-WD40 ternary complex and its regulatory role in anthocyanin biosynthesis pathway, focusing on the regulation mechanism of several important model plants by MYB-bHIM-WD40 complex.

Ammonium-dependent regulation of ammonium transporter ZmAMT1s expression conferred by glutamine levels in roots of maize

In maize,two root epidermis-expressed ammonium transporters ZmAMT1;1a and ZmAMT1;3 play major roles in highaffinity ammonium uptake.However,the transcriptional regulation of ZmAMT1s in roots for ensuring optimal ammonium acquisition remains largely unknown.Here,using a split root system we showed that ZmAMT1;1a and ZmAMT1;3transcript levels were induced by localized ammonium supply to nitrogen-deficient roots.This enhanced expression of Zm AMT1s correlated with increases in ^(15)NH_(4)^(+)influx rates and tissue glutamine concentrations in roots.When ammonium was supplied together with methionine sulfoximine,an inhibitor of glutamine synthase,ammonium-induced expression of ZmAMT1s disappeared,suggesting that glutamine rather than ammonium itself regulated ZmAMT1s expression.When glutamine was supplied to nitrogen-deficient roots,expression levels of ZmAMT1s were enhanced,and negative feedback regulation could subsequently occur by supply of glutamine at a high level.Thus,our results indicated an ammonium-dependent regulation of ZmAMT1s at transcript levels,and a dual role of glutamine was suggested in the regulation of ammonium uptake in maize roots.

Up-regulation of VLDL Receptor Expression and Its Signaling Pathway Induced by VLDL and β-VLDL

Very low density lipoprotein receptor （VLDLR） is thought to participate in the pathogenesis of atherosclerosis induced by VLDL and β-VLDL. The present study was undertaken to elucidate the effects of VLDL and β-VLDL on VLDLR expression and its signaling pathway. RAW264.7 cells were incubated with VLDL and β-VLDL. The expression of VLDLR mRNA was detected by RT-PCR. The transcriptional activity of VLDLR gene was detected in recombinant plasmid pGL4.2VR-luciferase transfected RAW264.7. Western blot assay was used to detect the changes of phosphorylated ERK1/2 protein. Inhibitors or activators were used to observe the signal pathway involving VLDLR expression regulation. The results showed that VLDL and β-VLDL stimulated ERK1/2 activity in a PKC-dependent manner. VLDL or β-VLDL-induced VLDLR expression on macrophages was extremely abolished by inhibitors ERK1/2 or PKC. Our findings revealed that VLDL or β-VLDL-induced VLDLR expression via PKC/ERK cascades and the effect was linked to the transcriptional activation of VLDLR gene promoter.