scholarly journals MIST1 and PTF1 Collaborate in Feed-Forward Regulatory Loops That Maintain the Pancreatic Acinar Phenotype in Adult Mice

2016 ◽  
Vol 36 (23) ◽  
pp. 2945-2955 ◽  
Author(s):  
Mei Jiang ◽  
Ana C. Azevedo-Pouly ◽  
Tye G. Deering ◽  
Chinh Q. Hoang ◽  
Daniel DiRenzo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Acinar Cell ◽  
Pancreatic Acinar Cell ◽  
Physical Interaction ◽  
Transcriptional Enhancer ◽  
Feed Forward ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Much remains unknown regarding the regulatory networks formed by transcription factors in mature, differentiated mammalian cells in vivo , despite many studies of individual DNA-binding transcription factors. We report a constellation of feed-forward loops formed by the pancreatic transcription factors MIST1 and PTF1 that govern the differentiated phenotype of the adult pancreatic acinar cell. PTF1 is an atypical basic helix-loop-helix transcription factor complex of pancreatic acinar cells and is critical to acinar cell fate specification and differentiation. MIST1, also a basic helix-loop-helix transcription factor, enhances the formation and maintenance of the specialized phenotype of professional secretory cells. The MIST1 and PTF1 collaboration controls a wide range of specialized cellular processes, including secretory protein synthesis and processing, exocytosis, and homeostasis of the endoplasmic reticulum. PTF1 drives Mist1 transcription, and MIST1 and PTF1 bind and drive the transcription of over 100 downstream acinar genes. PTF1 binds two canonical bipartite sites within a 0.7-kb transcriptional enhancer upstream of Mist1 that are essential for the activity of the enhancer in vivo . MIST1 and PTF1 coregulate target genes synergistically or additively, depending on the target transcriptional enhancer. The frequent close binding proximity of PTF1 and MIST1 in pancreatic acinar cell chromatin implies extensive collaboration although the collaboration is not dependent on a stable physical interaction.

scholarly journals Basic Helix-Loop-Helix (bHLH) Transcription Factors Regulate a Wide Range of Functions in Arabidopsis

2021 ◽  
Vol 22 (13) ◽  
pp. 7152
Author(s):  
Yaqi Hao ◽  
Xiumei Zong ◽  
Pan Ren ◽  
Yuqi Qian ◽  
Aigen Fu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Gene Families ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Range Of Functions ◽  
Eukaryotic Organisms

The basic helix-loop-helix (bHLH) transcription factor family is one of the largest transcription factor gene families in Arabidopsis thaliana, and contains a bHLH motif that is highly conserved throughout eukaryotic organisms. Members of this family have two conserved motifs, a basic DNA binding region and a helix-loop-helix (HLH) region. These proteins containing bHLH domain usually act as homo- or heterodimers to regulate the expression of their target genes, which are involved in many physiological processes and have a broad range of functions in biosynthesis, metabolism and transduction of plant hormones. Although there are a number of articles on different aspects to provide detailed information on this family in plants, an overall summary is not available. In this review, we summarize various aspects of related studies that provide an overview of insights into the pleiotropic regulatory roles of these transcription factors in plant growth and development, stress response, biochemical functions and the web of signaling networks. We then provide an overview of the functional profile of the bHLH family and the regulatory mechanisms of other proteins.

scholarly journals Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation

2020 ◽  
Vol 48 (9) ◽  
pp. 4839-4857 ◽  
Author(s):  
Miriam Wedel ◽  
Franziska Fröb ◽  
Olga Elsesser ◽  
Marie-Theres Wittmann ◽  
D Chichung Lie ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Physical Interaction ◽  
Functional Studies ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Mouse Mutants ◽  
Id Proteins ◽  
A Cell ◽  
Oligodendrocyte Development

Abstract Development of oligodendrocytes and myelin formation in the vertebrate central nervous system is under control of several basic helix-loop-helix transcription factors such as Olig2, Ascl1, Hes5 and the Id proteins. The class I basic helix-loop-helix proteins Tcf3, Tcf4 and Tcf12 represent potential heterodimerization partners and functional modulators for all, but have not been investigated in oligodendrocytes so far. Using mouse mutants, organotypic slice and primary cell cultures we here show that Tcf4 is required in a cell-autonomous manner for proper terminal differentiation and myelination in vivo and ex vivo. Partial compensation is provided by the paralogous Tcf3, but not Tcf12. On the mechanistic level Tcf4 was identified as the preferred heterodimerization partner of the central regulator of oligodendrocyte development Olig2. Both genetic studies in the mouse as well as functional studies on enhancer regions of myelin genes confirmed the relevance of this physical interaction for oligodendrocyte differentiation. Considering that alterations in TCF4 are associated with syndromic and non-syndromic forms of intellectual disability, schizophrenia and autism in humans, our findings point to the possibility of an oligodendroglial contribution to these disorders.

scholarly journals Specific Protein-Protein Interaction between Basic Helix-Loop-Helix Transcription Factors and Homeoproteins of the Pitx Family

2000 ◽  
Vol 20 (13) ◽  
pp. 4826-4837 ◽  
Author(s):  
Gino Poulin ◽  
Mélanie Lebel ◽  
Michel Chamberland ◽  
Francois W. Paradis ◽  
Jacques Drouin
Keyword(s):  
Transcription Factors ◽  
Critical Role ◽  
Specific Protein ◽  
Physical Interaction ◽  
Protein Protein Interaction ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Factors ◽  
Pomc Gene ◽  
Bhlh Transcription Factors

ABSTRACT Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression of NeuroD1 in pituitary corticotroph cells and a direct physical interaction between bHLH heterodimers and Pitx1 that results in transcriptional synergism. The interaction between the bHLH and homeodomains is restricted to ubiquitous (class A) bHLH and to the Pitx subfamily. Since bHLH heterodimers interact with Pitx factors through their ubiquitous moiety, this mechanism may be implicated in other developmental processes involving bHLH factors, such as neurogenesis and myogenesis.

scholarly journals The Basic Helix-Loop-Helix Transcription Factor NeuroD1 Facilitates Interaction of Sp1 with the Secretin Gene Enhancer

2007 ◽  
Vol 27 (22) ◽  
pp. 7839-7847 ◽  
Author(s):  
Subir K. Ray ◽  
Andrew B. Leiter
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Target Genes ◽  
Zinc Fingers ◽  
Homeodomain Proteins ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Gene Enhancer ◽  
Genes Encoding

ABSTRACT The basic helix-loop-helix transcription factor NeuroD1 is required for late events in neuronal differentiation, for maturation of pancreatic β cells, and for terminal differentiation of enteroendocrine cells expressing the hormone secretin. NeuroD1-null mice demonstrated that this protein is essential for expression of the secretin gene in the murine intestine, and yet it is a relatively weak transcriptional activator by itself. The present study shows that Sp1 and NeuroD1 synergistically activate transcription of the secretin gene. NeuroD1, but not its widely expressed dimerization partner E12, physically interacts with the C-terminal 167 amino acids of Sp1, which include its DNA binding zinc fingers. NeuroD1 stabilizes Sp1 DNA binding to an adjacent Sp1 binding site on the promoter to generate a higher-order DNA-protein complex containing both proteins and facilitates Sp1 occupancy of the secretin promoter in vivo. NeuroD-dependent transcription of the genes encoding the hormones insulin and proopiomelanocortin is potentiated by lineage-specific homeodomain proteins. The stabilization of binding of the widely expressed transcription factor Sp1 to the secretin promoter by NeuroD represents a distinct mechanism from other NeuroD target genes for increasing NeuroD-dependent transcription.

The basic-helix-loop-helix protein pod1 is critically important for kidney and lung organogenesis

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5771-5783 ◽  
Author(s):  
S.E. Quaggin ◽  
L. Schwartz ◽  
S. Cui ◽  
P. Igarashi ◽  
J. Deimling ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Perinatal Period ◽  
Branching Morphogenesis ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Kidney Morphogenesis

Epithelial-mesenchymal interactions are required for the development of all solid organs but few molecular mechanisms that underlie these interactions have been identified. Pod1 is a basic-helix-loop-helix (bHLH) transcription factor that is highly expressed in the mesenchyme of developing organs that include the lung, kidney, gut and heart and in glomerular visceral epithelial cells (podocytes). To determine the function of Pod1 in vivo, we have generated a lacZ-expressing null Pod1 allele. Null mutant mice are born but die in the perinatal period with severely hypoplastic lungs and kidneys that lack alveoli and mature glomeruli. Although Pod1 is exclusively expressed in the mesenchyme and podocytes, major defects are observed in the adjacent epithelia and include abnormalities in epithelial differentiation and branching morphogenesis. Pod1 therefore appears to be essential for regulating properties of the mesenchyme that are critically important for lung and kidney morphogenesis. Defects specific to later specialized cell types where Pod1 is expressed, such as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis.

scholarly journals Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif

2019 ◽  
Vol 48 (2) ◽  
pp. 934-948 ◽  
Author(s):  
Vivian Pogenberg ◽  
Josué Ballesteros-Álvarez ◽  
Romana Schober ◽  
Ingibjörg Sigvaldadóttir ◽  
Agnieszka Obarska-Kosinska ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
High Resolution ◽  
Nuclear Localization ◽  
Leucine Zipper ◽  
Coiled Coil ◽  
Fundamental Difference ◽  
Wild Type ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Abstract Interrupted dimeric coiled coil segments are found in a broad range of proteins and generally confer selective functional properties such as binding to specific ligands. However, there is only one documented case of a basic-helix–loop–helix leucine zipper transcription factor—microphthalmia-associated transcription factor (MITF)—in which an insertion of a three-residue stammer serves as a determinant of conditional partner selectivity. To unravel the molecular principles of this selectivity, we have analyzed the high-resolution structures of stammer-containing MITF and an engineered stammer-less MITF variant, which comprises an uninterrupted symmetric coiled coil. Despite this fundamental difference, both MITF structures reveal identical flanking in-phase coiled coil arrangements, gained by helical over-winding and local asymmetry in wild-type MITF across the stammer region. These conserved structural properties allow the maintenance of a proper functional readout in terms of nuclear localization and binding to specific DNA-response motifs regardless of the presence of the stammer. By contrast, MITF heterodimer formation with other bHLH-Zip transcription factors is only permissive when both factors contain either the same type of inserted stammer or no insert. Our data illustrate a unique principle of conditional partner selectivity within the wide arsenal of transcription factors with specific partner-dependent functional readouts.

Determination versus differentiation and the MyoD family of transcription factors

1995 ◽  
Vol 73 (9-10) ◽  
pp. 723-732 ◽  
Author(s):  
Lynn A. Megeney ◽  
Michael A. Rudnicki
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Sequence Homology ◽  
Expression Patterns ◽  
Myogenic Regulatory Factors ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

The myogenic regulatory factors (MRFs) form a family of basic helix–loop–helix transcription factors consisting of Myf-5, MyoD, myogenin, and MRF4. The MRFs play key regulatory roles in the development of skeletal muscle during embryogenesis. Sequence homology, expression patterns, and genetargeting experiments have revealed a two-tiered subclassification within the MRF family. Myf-5 and MyoD are more homologous to one another than to the others, are expressed in myoblasts before differentiation, and are required for the determination or survival of muscle progenitor cells. By contrast, myogenin and MRF4 are more homologous to one another than to the others and are expressed upon differentiation, and myogenin is required in vivo as a differentiation factor while the role of MRF4 remains unclear. On this basis, MyoD and Myf-5 are classified as primary MRFs, as they are required for the determination of myoblasts, and myogenin and MRF4 are classified as secondary MRFs, as they likely function during terminal differentiation.Key words: MyoD, Myf-5, myogenin, MRF4, skeletal muscle.

scholarly journals Basic Helix-Loop-Helix Transcription Factor Heterocomplex of Yas1p and Yas2p Regulates Cytochrome P450 Expression in Response to Alkanes in the Yeast Yarrowia lipolytica

2007 ◽  
Vol 6 (4) ◽  
pp. 734-743 ◽  
Author(s):  
Setsu Endoh-Yamagami ◽  
Kiyoshi Hirakawa ◽  
Daisuke Morioka ◽  
Ryouichi Fukuda ◽  
Akinori Ohta
Keyword(s):  
Cytochrome P450 ◽  
Transcription Factors ◽  
Yarrowia Lipolytica ◽  
Bhlh Protein ◽  
Genome Database ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Transcription Factors

ABSTRACT The expression of the ALK1 gene, which encodes cytochrome P450, catalyzing the first step of alkane oxidation in the alkane-assimilating yeast Yarrowia lipolytica, is highly regulated and can be induced by alkanes. Previously, we identified a cis-acting element (alkane-responsive element 1 [ARE1]) in the ALK1 promoter. We showed that a basic helix-loop-helix (bHLH) protein, Yas1p, binds to ARE1 in vivo and mediates alkane-dependent transcription induction. Yas1p, however, does not bind to ARE1 by itself in vitro, suggesting that Yas1p requires another bHLH protein partner for its DNA binding, as many bHLH transcription factors function by forming heterodimers. To identify such a binding partner of Yas1p, here we screened open reading frames encoding proteins with the bHLH motif from the Y. lipolytica genome database and identified the YAS2 gene. The deletion of the YAS2 gene abolished the alkane-responsive induction of ALK1 transcription and the growth of the yeast on alkanes. We revealed that Yas2p has transactivation activity. Furthermore, Yas1p and Yas2p formed a protein complex that was required for the binding of these proteins to ARE1. These findings allow us to postulate a model in which bHLH transcription factors Yas1p and Yas2p form a heterocomplex and mediate the transcription induction in response to alkanes.

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