Challenges of Decoding Transcription Factor Dynamics in Terms of Gene Regulation

Technological advances are continually improving our ability to obtain more accurate views about the inner workings of biological systems. One such rapidly evolving area is single cell biology, and in particular gene expression and its regulation by transcription factors in response to intrinsic and extrinsic factors. Regarding the study of transcription factors, we discuss some of the promises and pitfalls associated with investigating how individual cells regulate gene expression through modulation of transcription factor activities. Specifically, we discuss four leading experimental approaches, the data that can be obtained from each, and important considerations that investigators should be aware of when drawing conclusions from such data.

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Transcription Factor ANAC074 Binds to NRS1, NRS2, or MybSt1 Element in Addition to the NACRS to Regulate Gene Expression

International Journal of Molecular Sciences ◽

10.3390/ijms19103271 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3271

Author(s):

Lin He ◽

Jingyu Xu ◽

Yucheng Wang ◽

Kejun Yang

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Transcription Factor ◽

Transcription Factors ◽

Biological Processes ◽

Regulate Gene Expression ◽

Cis Element ◽

Stress Responsive Genes ◽

Regulate Gene ◽

Gus Assays

NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in many biological processes, and mainly bind to the NACRS with core sequences “CACG” or “CATGTG” to regulate gene expression. However, whether NAC proteins can bind to other motifs without these core sequences remains unknown. In this study, we employed a Transcription Factor-Centered Yeast one Hybrid (TF-Centered Y1H) screen to study the motifs recognized by ANAC074. In addition to the NACRS core cis-element, we identified that ANAC074 could bind to MybSt1, NRS1, and NRS2. Y1H and GUS assays showed that ANAC074 could bind the promoters of ethylene responsive genes and stress responsive genes via the NRS1, NRS2, or MybSt1 element. ChIP study further confirmed that the bindings of ANAC074 to MybSt1, NRS1, and NRS2 actually occurred in Arabidopsis. Furthermore, ten NAC proteins from different NAC subfamilies in Arabidopsis thaliana were selected and confirmed to bind to the MybSt1, NRS1, and NRS2 motifs, indicating that they are recognized commonly by NACs. These findings will help us to further reveal the functions of NAC proteins.

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Arabidopsis heat shock transcription factor HSFA7b positively mediates salt stress tolerance by binding to an E-box-like motif to regulate gene expression

Journal of Experimental Botany ◽

10.1093/jxb/erz261 ◽

2019 ◽

Vol 70 (19) ◽

pp. 5355-5374 ◽

Cited By ~ 11

Author(s):

Dandan Zang ◽

Jingxin Wang ◽

Xin Zhang ◽

Zhujun Liu ◽

Yucheng Wang

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Heat Shock ◽

Salt Tolerance ◽

Stress Responses ◽

Ion Homeostasis ◽

Cellulose Synthase ◽

Regulate Gene Expression ◽

E Box ◽

Regulate Gene

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.

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The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression

Scientific Reports ◽

10.1038/srep12983 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 32

Author(s):

Yiguo Zhang ◽

Shaojun Li ◽

Yuancai Xiang ◽

Lu Qiu ◽

Huakan Zhao ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Regulate Gene Expression ◽

Regulate Gene

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microRNAs: a new frontier in kallikrein research

Biological Chemistry ◽

10.1515/bc.2008.068 ◽

2008 ◽

Vol 389 (6) ◽

Cited By ~ 19

Author(s):

George M. Yousef

Keyword(s):

Gene Expression ◽

Human Tissue ◽

In Silico ◽

Regulatory Mechanism ◽

Transcriptional Level ◽

Regulate Gene Expression ◽

New Frontier ◽

Experimental Approaches ◽

Non Coding Rnas ◽

Regulate Gene

Abstract microRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression. Rapidly accumulating evidence has revealed that miRNAs are associated with cancer. The human tissue kalli-krein gene family is the largest contiguous family of proteases in the human genome, containing 15 genes. Many kallikreins have been reported as potential tumor markers. In this review, recent bioinformatics and experimental evidence is presented indicating that kallikreins are potential miRNA targets. The available experimental approaches to investigate these interactions and the potential diagnostic and therapeutic applications are also discussed. miRNAs represent a possible regulatory mechanism for controlling kallikrein expression at the post-transcriptional level. Many miRNAs were predicted to target kallikreins and a single miRNA can target more than one kallikrein. Recent evidence suggests that miRNAs can also exert ‘quantitative’ control of kallikreins by utilizing multiple targeting sites in the kallikrein mRNA. More research is needed to experimentally verify the in silico predictions and to investigate the possible role in tumor initiation and/or progression.

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The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila

Development ◽

10.1242/dev.121.10.3187 ◽

1995 ◽

Vol 121 (10) ◽

pp. 3187-3195 ◽

Cited By ~ 53

Author(s):

E.P. Spana ◽

C.Q. Doe

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Cell Fate ◽

Daughter Cell ◽

Cell Cortex ◽

Cell Fates ◽

Extrinsic Factors ◽

Cortical Localization ◽

Ganglion Mother Cell ◽

Intrinsic And Extrinsic Factors

Both intrinsic and extrinsic factors are known to regulate sibling cell fate. Here we describe a novel mechanism for the asymmetric localization of a transcription factor to one daughter cell at mitosis. The Drosophila CNS develops from asymmetrically dividing neuroblasts, which give rise to a large neuroblast and a smaller ganglion mother cell (GMC). The prospero gene encodes a transcription factor necessary for proper GMC gene expression. We show that the prospero protein is synthesized in the neuroblast where it is localized to the F-actin cell cortex. At mitosis, prospero is asymmetrically localized to the budding GMC and excluded from the neuroblast. After cytokinesis, prospero is translocated from the GMC cortex into the nucleus. Asymmetric cortical localization of prospero in neuroblasts requires entry into mitosis; it does not depend on numb function. prospero is also observed in cortical crescents in dividing precursors of the peripheral nervous system and adult midgut. The asymmetric cortical localization of prospero at mitosis is a mechanism for rapidly establishing distinct sibling cell fates in the CNS and possibly other tissues.

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Nkx3.1 Functions as Para-transcription Factor to Regulate Gene Expression and Cell Proliferation in Non-cell Autonomous Manner

Journal of Biological Chemistry ◽

10.1074/jbc.m111.336909 ◽

2012 ◽

Vol 287 (21) ◽

pp. 17248-17256 ◽

Cited By ~ 8

Author(s):

Jian Zhou ◽

Li Qin ◽

Jean Ching-Yi Tien ◽

Li Gao ◽

Xian Chen ◽

...

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Transcription Factor ◽

Regulate Gene Expression ◽

Regulate Gene

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TFAP2 paralogs pioneer chromatin access for MITF and directly inhibit genes associated with cell migration

10.1101/2021.11.23.469757 ◽

2021 ◽

Author(s):

Colin Kenny ◽

Ramile Dilshat ◽

Hannah Seberg ◽

Eric Van Otterloo ◽

Gregory Bonde ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Cell Types ◽

Chromatin Accessibility ◽

Wild Type ◽

Regulate Gene Expression ◽

Enhancer Binding Protein ◽

Pioneer Factors ◽

Regulate Gene ◽

Do So

Transcription factors in the Activating-enhancer-binding Protein 2 (TFAP2) family redundantly regulate gene expression in melanocytes and melanoma. Previous ChIP-seq experiments indicate that TFAP2A and Microphthalmia-associated Transcription Factor (MITF), a master regulator in these cell types, co-activate enhancers of genes promoting pigmentation. Evidence that TFAP2 paralogs can serve as pioneer factors supports the possibility that TFAP2 facilitates MITF binding at co-bound enhancers, although this model has not been tested. In addition, while MITF and TFAP2 paralogs both appear to repress genes that promote invasion, whether they do so by co-repressing enhancers is unknown. To address these questions we evaluated gene expression, chromatin accessibility, TFAP2A and MITF binding, and chromatin marks characteristic of active enhancers in SK-MEL-28 melanoma cells that were wild-type or deleted of the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C (i.e., TFAP2-KO cells). Integrated analyses revealed distinct subsets of enhancers bound by TFAP2A in WT cells that are inactivated and activated, respectively, in TFAP2-KO cells. At enhancers bound by both MITF and TFAP2A, MITF is generally lost in TFAP2A/TFAP2C double mutants, but not vice versa, implying TFAP2 pioneers chromatin access for MITF. There is a strong correlation between the sets of genes inhibited by MITF and TFAP2, although we did not find evidence that TFAP2 and MITF inhibit enhancers cooperatively. The findings imply that MITF and TFAP2 paralogs cooperatively affect the melanoma phenotype.

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The Clock Protein CCA1 and the bZIP Transcription Factor HY5 Physically Interact to Regulate Gene Expression in Arabidopsis

Molecular Plant ◽

10.1093/mp/ssm005 ◽

2008 ◽

Vol 1 (1) ◽

pp. 58-67 ◽

Cited By ~ 51

Author(s):

Christos Andronis ◽

Simon Barak ◽

Stephen M. Knowles ◽

Shoji Sugano ◽

Elaine M. Tobin

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Bzip Transcription Factor ◽

Regulate Gene Expression ◽

Clock Protein ◽

Regulate Gene

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Interaction of OIP5-AS1 with MEF2C mRNA promotes myogenic gene expression

Nucleic Acids Research ◽

10.1093/nar/gkaa1151 ◽

2020 ◽

Vol 48 (22) ◽

pp. 12943-12956

Author(s):

Jen-Hao Yang ◽

Ming-Wen Chang ◽

Poonam R Pandey ◽

Dimitrios Tsitsipatis ◽

Xiaoling Yang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Muscle Regeneration ◽

Muscle Development ◽

Rna Binding ◽

Myogenic Differentiation ◽

Binding Protein ◽

Rna Binding Protein ◽

Regulate Gene Expression ◽

Regulate Gene

Abstract Long noncoding (lnc)RNAs potently regulate gene expression programs in physiology and disease. Here, we describe a key function for lncRNA OIP5-AS1 in myogenesis, the process whereby myoblasts differentiate into myotubes during muscle development and muscle regeneration after injury. In human myoblasts, OIP5-AS1 levels increased robustly early in myogenesis, and its loss attenuated myogenic differentiation and potently reduced the levels of the myogenic transcription factor MEF2C. This effect relied upon the partial complementarity of OIP5-AS1 with MEF2C mRNA and the presence of HuR, an RNA-binding protein (RBP) with affinity for both transcripts. Remarkably, HuR binding to MEF2C mRNA, which stabilized MEF2C mRNA and increased MEF2C abundance, was lost after OIP5-AS1 silencing, suggesting that OIP5-AS1 might serve as a scaffold to enhance HuR binding to MEF2C mRNA, in turn increasing MEF2C production. These results highlight a mechanism whereby a lncRNA promotes myogenesis by enhancing the interaction of an RBP and a myogenic mRNA.

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