An Endocrine-Exocrine Switch in the Activity of the Pancreatic Homeodomain Protein PDX1 through Formation of a Trimeric Complex with PBX1b and MRG1 (MEIS2)

Swift, Galvin H.; Liu, Ying; Rose, Scott D.; Bischof, Larry J.; Steelman, Scott; Buchberg, Arthur M.; Wright, Christopher V.E.; MacDonald, Raymond J.

doi:10.1128/mcb.18.9.5109

Cited by 163 publications

(164 citation statements)

References 88 publications

(108 reference statements)

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…A switch in target gene regulation from repression to activation has been shown to occur when a monomeric instead of a heterodimeric Hox transcription factor binds a target gene (52). Further, differential cofactor binding can also switch the function of the HOX transcription factor from activation to repression at different stages of development (42,44).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Repression of Peri-Implantation EMX2 Expression in Mammalian Reproduction by HOXA10

Troy

Daftary

Bagot

et al. 2003

Molecular and Cellular Biology

122

View full text Add to dashboard Cite

HOXA10 is necessary for mammalian reproduction; however, its transcriptional targets are not completely defined. EMX2, a divergent homeobox gene, is necessary for urogenital tract development. In these studies we identify and characterize the regulation of EMX2 by HOXA10. By using Northern analysis and in situ hybridization, we found that EMX2 is expressed in the adult urogenital tract in an inverse temporal pattern from HOXA10

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional Repression of Peri-Implantation EMX2 Expression in Mammalian Reproduction by HOXA10

Troy

Daftary

Bagot

et al. 2003

Molecular and Cellular Biology

122

View full text Add to dashboard Cite

show abstract

“…Therefore, maintaining the low level of Pdx1 expression in the acinar cells is required for their formation and differentiation (Holland et al, 2002;Hale et al, 2005). In acinar cells, Pdx1 forms a trimeric complex with Pbx1 and Meis2, which controls the nature of the transcriptional activity of PDX1 in acinar versus endocrine cells (Swift et al, 1998). The Pdx1-Pbx1-Meis2 trimeric complex cooperates with PTF1 to activate the acinar-specific elastase1 promoter (Liu et al, 2001).…”

Section: Pdx1mentioning

confidence: 99%

Pancreas organogenesis: From bud to plexus to gland

Pan

Wright

2011

Developmental Dynamics

528

594

View full text Add to dashboard Cite

Pancreas oganogenesis comprises a coordinated and highly complex interplay of signaling events and transcriptional networks that guide a step-wise process of organ development from early bud specification all the way to the final mature organ state. Extensive research on pancreas development over the last few years, largely driven by a translational potential for pancreatic diseases (diabetes, pancreatic cancer, and so on), is markedly advancing our knowledge of these processes. It is a tenable goal that we will one day have a clear, complete picture of the transcriptional and signaling codes that control the entire organogenetic process, allowing us to apply this knowledge in a therapeutic context, by generating replacement cells in vitro, or perhaps one day to the whole organ in vivo. This review summarizes findings in the past 5 years that we feel are amongst the most significant in contributing to the deeper understanding of pancreas development. Rather than try to cover all aspects comprehensively, we have chosen to highlight interesting new concepts, and to discuss provocatively some of the more controversial findings or proposals. At the end of the review, we include a perspective section on how the whole pancreas differentiation process might be able to be unwound in a regulated fashion, or redirected, and suggest linkages to the possible reprogramming of other pancreatic cell-types in vivo, and to the optimization of the forward-directed-differentiation of human embryonic stem cells (hESC), or induced pluripotential cells (iPSC), towards mature b-cells. Developmental Dynamics 240:530-565,

show abstract

“…These interacting factors include bHLH proteins that bind to Eboxes (BETA2/NeuroD1 and E2A proteins) [122,123,140,141], the basic leucine zipper factor MafA that binds to the C-box [73,142], the homeodomain proteins Pbx1 and MEIS2 [47,48,143,144], and high mobility group (HMG) proteins that bind to the DNA backbone [123]. The free energy gained from these interactions may increase the likelihood that Pdx1 targets genes with binding sites for these factors [123,144].…”

Section: Mechanisms Of Transcriptional Regulation By Pdx1mentioning

confidence: 99%

A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis

Babu

Deering

Mirmira

2007

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Emerging evidence over the past decade indicates a central role for transcription factors in the embryonic development of pancreatic islets and the consequent maintenance of normal glucose homeostasis. Pancreatic and duodenal homeobox 1 (Pdx1) is the best studied and perhaps most important of these factors. Whereas deletion or inactivating mutations of the Pdx1 gene causes whole pancreas agenesis in both mice and humans, even haploinsufficiency of the gene or alterations in its expression in mature islet cells causes substantial impairments in glucose tolerance and the development of a late-onset form of diabetes known as maturity onset diabetes of the young. The study of Pdx1 has revealed crucial phenotypic interrelationships of the varied cell types within the pancreas, particularly as these impinge upon cellular differentiation in the embryo and neogenesis and regeneration in the adult. In this review, we describe the actions of Pdx1 in the developing and mature pancreas and attempt to unify these actions with its known roles in modulating transcriptional complex formation and chromatin structure at the molecular genetic level.

show abstract

An Endocrine-Exocrine Switch in the Activity of the Pancreatic Homeodomain Protein PDX1 through Formation of a Trimeric Complex with PBX1b and MRG1 (MEIS2)

Cited by 163 publications

References 88 publications

Transcriptional Repression of Peri-Implantation EMX2 Expression in Mammalian Reproduction by HOXA10

Transcriptional Repression of Peri-Implantation EMX2 Expression in Mammalian Reproduction by HOXA10

Pancreas organogenesis: From bud to plexus to gland

A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis

Contact Info

Product

Resources

About