Bookmarking by Non-pioneer Transcription Factors during Liver Development Establishes Competence for Future Gene Activation

During liver organogenesis, cellular transcriptional profiles are constantly reshaped by the action of hepatic transcriptional regulators, including FoxA1-3, GATA4/6, HNF1α/β, HNF4α, HNF6, OC-2, C/EBPα/β, Hex, and Prox1. These factors are crucial for the activation of hepatic genes that, in the context of compact chromatin, cannot access their targets. The initial opening of highly condensed chromatin is executed by a special class of transcription factors known as pioneer factors. They bind and destabilize highly condensed chromatin and facilitate access to other “non-pioneer” factors. The association of target genes with pioneer and non-pioneer transcription factors takes place long before gene activation. In this way, the underlying gene regulatory regions are marked for future activation. The process is called “bookmarking”, which confers transcriptional competence on target genes. Developmental bookmarking is accompanied by a dynamic maturation process, which prepares the genomic loci for stable and efficient transcription. Stable hepatic expression profiles are maintained during development and adulthood by the constant availability of the main regulators. This is achieved by a self-sustaining regulatory network that is established by complex cross-regulatory interactions between the major regulators. This network gradually grows during liver development and provides an epigenetic memory mechanism for safeguarding the optimal expression of the regulators.

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Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize

10.1101/2021.02.05.429970 ◽

2021 ◽

Author(s):

Mingxia Zhao ◽

Zhao Peng ◽

Yang Qin ◽

Ling Zhang ◽

Bin Tian ◽

...

Keyword(s):

Gene Regulation ◽

Transcription Factor ◽

Transcription Factors ◽

Protein Delivery ◽

Graphical Model ◽

Gene Activation ◽

Cuticular Wax ◽

Host Cells ◽

Myb Transcription Factor ◽

Leaf Phenotype

ABSTRACTCellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the γ-proteobacterium genus Xanthomonas and secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen, Xanthomonas vasicola pv. vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize gene glossy3 (gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146 gl3 downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68 gl3 downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from the gl3 downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.

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DNA Binding and Gene Activation Properties of the Nmp4 Nuclear Matrix Transcription Factors

Journal of Biological Chemistry ◽

10.1074/jbc.m107496200 ◽

2002 ◽

Vol 277 (18) ◽

pp. 16153-16159 ◽

Cited By ~ 21

Author(s):

Kitti Torrungruang ◽

Marta Alvarez ◽

Rita Shah ◽

Jude E. Onyia ◽

Simon J. Rhodes ◽

...

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Nuclear Matrix ◽

Gene Activation

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Transcript profiling of bovine embryos implicates specific transcription factors in the maternal-to-embryo transition

Biology of Reproduction ◽

10.1093/biolre/ioz209 ◽

2019 ◽

Vol 102 (3) ◽

pp. 671-679 ◽

Cited By ~ 3

Author(s):

Yanina S Bogliotti ◽

Nhi Chung ◽

Erika E Paulson ◽

James Chitwood ◽

Michelle Halstead ◽

...

Keyword(s):

Transcription Factors ◽

Rna Polymerase Ii ◽

Gene Activation ◽

Preimplantation Embryos ◽

Maternal Mrna ◽

Embryonic Genome ◽

Maternal Mrnas ◽

Low Levels ◽

Genome Activation ◽

Further Development

Abstract Full-grown oocytes are transcriptionally quiescent. Following maturation and fertilization, the early stages of embryonic development occur in the absence (or low levels) of transcription that results in a period of development relying on maternally derived products (e.g., mRNAs and proteins). Two critical steps occur during the transition from maternal to embryo control of development: maternal mRNA clearance and embryonic genome activation with an associated dramatic reprogramming of gene expression required for further development. By combining an RNA polymerase II inhibitor with RNA sequencing, we were able not only to distinguish maternally derived from embryonic transcripts in bovine preimplantation embryos but also to establish that embryonic gene activation is required for clearance of maternal mRNAs as well as to identify putative transcription factors that are likely critical for early bovine development.

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Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors

FEBS Letters ◽

10.1016/s0014-5793(03)01446-7 ◽

2003 ◽

Vol 556 (1-3) ◽

pp. 236-244 ◽

Cited By ~ 87

Author(s):

Andreas Ludwig ◽

Stephan Rehberg ◽

Michael Wegner

Keyword(s):

Transcription Factors ◽

Gene Activation ◽

Specific Expression ◽

Dopachrome Tautomerase

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HNF-1α and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00074.2003 ◽

2003 ◽

Vol 285 (1) ◽

pp. G62-G72 ◽

Cited By ~ 31

Author(s):

Joyce K. Divine ◽

Sean P. McCaul ◽

Theodore C. Simon

Keyword(s):

Transcription Factors ◽

Gene Activation ◽

The Other ◽

Wild Type ◽

Critical Determinant ◽

Fatty Acid Binding ◽

Hepatic Expression ◽

Synergistic Activation ◽

Five Factors

Hepatocyte nuclear factor (HNF)-1α plays a central role in intestinal and hepatic gene regulation and is required for hepatic expression of the liver fatty acid binding protein gene ( Fabpl). An Fabpl transgene was directly activated through cognate sites by HNF-1α and HNF-1β, as well as five other endodermal factors: CDX-1, C/EBPβ, GATA-4, FoxA2, and HNF-4α. HNF-1α activated the Fabpl transgene by as much as 60-fold greater in the presence of the other five endodermal factors than in their absence, accounting for up to one-half the total transgene activation by the group of six factors. This degree of synergistic interaction suggests that multifactor cooperativity is a critical determinant of endodermal gene activation by HNF-1α. Mutations in HNF-1α that result in maturity onset diabetes of the young (MODY3) provide evidence for the in vivo significance of these synergistic interactions. An R131Q HNF-1α MODY3 mutant exhibits complete loss of synergistic activation in concert with the other endodermal transcription factors despite wild-type transactivation ability in their absence. Furthermore, whereas wild-type HNF-1α exhibited pairwise cooperative synergy with each of the other five factors, the R131Q mutant could synergize only with GATA-4 and C/EBPβ. Selective loss of synergy with other endodermal transcription factors accompanied by retention of native transactivation ability in an HNF-1α MODY mutant suggests in vivo significance for cooperative synergy.

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A Role for Mediator Core in Limiting Coactivator Recruitment in Saccharomyces cerevisiae

Genetics ◽

10.1534/genetics.120.303254 ◽

2020 ◽

Vol 215 (2) ◽

pp. 407-420 ◽

Cited By ~ 1

Author(s):

Robert M. Yarrington ◽

Yaxin Yu ◽

Chao Yan ◽

Lu Bai ◽

David J. Stillman

Keyword(s):

Saccharomyces Cerevisiae ◽

Gene Regulation ◽

Transcription Factors ◽

Gene Activation ◽

Mediator Complex ◽

Transcriptional Coactivator ◽

The Core ◽

Link Type ◽

Upstream Activating Sequence ◽

Eukaryotic Organisms

Mediator is an essential, multisubunit complex that functions as a transcriptional coactivator in yeast and other eukaryotic organisms. Mediator has four conserved modules, Head, Middle, Tail, and Kinase, and has been implicated in nearly all aspects of gene regulation. The Tail module has been shown to recruit the Mediator complex to the enhancer or upstream activating sequence (UAS) regions of genes via interactions with transcription factors, and the Kinase module facilitates the transition of Mediator from the UAS/enhancer to the preinitiation complex via protein phosphorylation. Here, we analyze expression of the Saccharomyces cerevisiae HO gene using a sin4 Mediator Tail mutation that separates the Tail module from the rest of the complex; the sin4 mutation permits independent recruitment of the Tail module to promoters without the rest of Mediator. Significant increases in recruitment of the SWI/SNF and SAGA coactivators to the HO promoter UAS were observed in a sin4 mutant, along with increased gene activation. These results are consistent with recent studies that have suggested that the Kinase module functions negatively to inhibit activation by the Tail. However, we found that Kinase module mutations did not mimic the effect of a sin4 mutation on HO expression. This suggests that at HO the core Mediator complex (Middle and Head modules) must play a role in limiting Tail binding to the promoter UAS and gene activation. We propose that the core Mediator complex helps modulate Mediator binding to the UAS regions of genes to limit coactivator recruitment and ensure proper regulation of gene transcription.

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Modulation of Pseudomonas aeruginosa Quorum Sensing by Glutathione

Journal of Bacteriology ◽

10.1128/jb.00685-18 ◽

2019 ◽

Vol 201 (9) ◽

Cited By ~ 3

Author(s):

Hui Zhou ◽

Meizhen Wang ◽

Nicole E. Smalley ◽

Maxim Kostylev ◽

Amy L. Schaefer ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Transcription Factor ◽

Transcription Factors ◽

Quorum Sensing ◽

Cell Density ◽

Redox State ◽

Gene Activation ◽

Cellular Redox ◽

Content Type ◽

Cellular Redox State

ABSTRACT Pseudomonas aeruginosa uses quorum sensing (QS) to regulate the production of a battery of secreted products. At least some of these products are shared among the population and serve as public goods. When P. aeruginosa is grown on casein as the sole carbon and energy source, the QS-induced extracellular protease elastase is required for growth. We isolated a P. aeruginosa variant, which showed increased production of QS-induced factors after repeated transfers in casein broth. This variant, P. aeruginosa QS*, had a mutation in the glutathione synthesis gene gshA. We describe several experiments that show a gshA coding variant and glutathione affect the QS response. The P. aeruginosa QS transcription factor LasR has a redox-sensitive cysteine (C79). We report that GshA variant cells with a LasR C79S substitution show a similar QS response to that of wild-type P. aeruginosa. Surprisingly, it is not LasR but the QS transcription factor RhlR that is more active in bacteria containing the variant gshA. Our results demonstrate that QS integrates information about cell density and the cellular redox state via glutathione levels. IMPORTANCE Pseudomonas aeruginosa and other bacteria coordinate group behaviors using a chemical communication system called quorum sensing (QS). The QS system of P. aeruginosa is complex, with several regulators and signals. We show that decreased levels of glutathione lead to increased gene activation in P. aeruginosa, which did not occur in a strain carrying the redox-insensitive variant of a transcription factor. The ability of P. aeruginosa QS transcription factors to integrate information about cell density and cellular redox state shows these transcription factors can fine-tune levels of the gene products they control in response to at least two types of signals or cues.

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The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis

Scientific Reports ◽

10.1038/s41598-020-78629-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Annekarin Meyer ◽

Stefanie Herkt ◽

Heike Kunze-Schumacher ◽

Nicole Kohrs ◽

Julia Ringleb ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Malignant Disease ◽

Expression Patterns ◽

Gene Activation ◽

Erythroid Differentiation ◽

Mature Micrornas ◽

Gene Regulatory ◽

Regulatory Loop ◽

Transcriptional Complex

AbstractA network of gene regulatory factors such as transcription factors and microRNAs establish and maintain gene expression patterns during hematopoiesis. In this network, transcription factors regulate each other and are involved in regulatory loops with microRNAs. The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.

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Plenary Lecture 2 Transcription factors, regulatory elements and nutrient–gene communication

Proceedings of The Nutrition Society ◽

10.1017/s0029665109991790 ◽

2009 ◽

Vol 69 (1) ◽

pp. 91-94 ◽

Cited By ~ 5

Author(s):

Robert J. Cousins ◽

Tolunay B. Aydemir ◽

Louis A. Lichten

Keyword(s):

Transcription Factors ◽

Histone Acetylation ◽

Intracellular Transport ◽

Molecular Mechanisms ◽

Gene Activation ◽

Regulatory Elements ◽

Atp Citrate Lyase ◽

Signalling Molecules ◽

Citrate Lyase ◽

Normal Metabolism

Dramatic advances have been made in the understanding of the differing molecular mechanisms used by nutrients to regulate genes that are essential for their biological roles to carry out normal metabolism. Classical studies have focused on nutrients as ligands to activate specific transcription factors. New interest has focused on histone acetylation as a process for either global or limited gene activation and is the first mechanism to be discussed. Nuclear ATP-citrate lyase generates acetyl-CoA, which has been shown to have a role in the activation of specific genes via selective histone acetylation. Transcription factor acetylation may provide a second mode of control of nutrient-responsive gene transcription. The third mechanism relates to the availability of response elements within chromatin, which as well as the location of the elements in the gene may allow or prevent transcription. A fourth mechanism involves intracellular transport of Zn ions, which can orchestrate localized enzyme inhibition–activation. This process in turn influences signalling molecules that regulate gene expression. The examples provided in the present review point to a new level of complexity in understanding nutrient–gene communication.

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