Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a

Abstract Primitive and definitive erythropoiesis represent distinct hematopoietic programs that differ with respect to stage of development, transcriptional control, and growth regulation. Although these differences have been recognized for some time, the relationship of the two erythroid lineages to each other is not well established. We have used a model system based on the hematopoietic development of embryonic stem (ES) cells in culture to investigate the origins of the earliest hematopoietic populations. Using ES cells transduced with a retrovirus that overexpresses the HOX11 gene, we have established factor-dependent hematopoietic cell lines that represent novel stages of embryonic hematopoiesis. Analysis of three of these cell lines indicates that they differ with respect to cytokine responsiveness, cell surface markers, and developmental potential. Two of the cell lines, EBHX1 and EBHX11, display the unique capacity to generate both primitive and definitive erythroid progeny as defined by morphology and expression of βH1 and βmajor globin. The third line, EBHX14, has definitive erythroid and myeloid potential, but is unable to generate cells of the primitive erythroid lineage. Analysis of the cytokine responsiveness of the two lines with primitive erythroid potential has indicated that exposure to leukemia inhibitory factor (LIF) results in the upregulation of βH1 and a change in cellular morphology to that of primitive erythrocytes. These findings are the first demonstration of a clonal cell line with primitive and definitive hematopoietic potential and support the interpretation that these lineages may arise from a common precursor in embryonic life. In addition, they suggest that LIF could play a role in the regulation of primitive erythropoiesis. © 1998 by The American Society of Hematology.

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Overexpression of HOX11 Leads to the Immortalization of Embryonic Precursors With Both Primitive and Definitive Hematopoietic Potential

Blood ◽

10.1182/blood.v92.3.877.415k11_877_887 ◽

1998 ◽

Vol 92 (3) ◽

pp. 877-887 ◽

Cited By ~ 5

Author(s):

Gordon Keller ◽

Charles Wall ◽

Andrew Z.C. Fong ◽

Teresa S. Hawley ◽

Robert G. Hawley

Keyword(s):

Cell Lines ◽

Transcriptional Control ◽

Growth Regulation ◽

Es Cells ◽

Embryonic Stem ◽

Developmental Potential ◽

Stage Of Development ◽

Embryonic Life ◽

Cytokine Responsiveness ◽

American Society

Primitive and definitive erythropoiesis represent distinct hematopoietic programs that differ with respect to stage of development, transcriptional control, and growth regulation. Although these differences have been recognized for some time, the relationship of the two erythroid lineages to each other is not well established. We have used a model system based on the hematopoietic development of embryonic stem (ES) cells in culture to investigate the origins of the earliest hematopoietic populations. Using ES cells transduced with a retrovirus that overexpresses the HOX11 gene, we have established factor-dependent hematopoietic cell lines that represent novel stages of embryonic hematopoiesis. Analysis of three of these cell lines indicates that they differ with respect to cytokine responsiveness, cell surface markers, and developmental potential. Two of the cell lines, EBHX1 and EBHX11, display the unique capacity to generate both primitive and definitive erythroid progeny as defined by morphology and expression of βH1 and βmajor globin. The third line, EBHX14, has definitive erythroid and myeloid potential, but is unable to generate cells of the primitive erythroid lineage. Analysis of the cytokine responsiveness of the two lines with primitive erythroid potential has indicated that exposure to leukemia inhibitory factor (LIF) results in the upregulation of βH1 and a change in cellular morphology to that of primitive erythrocytes. These findings are the first demonstration of a clonal cell line with primitive and definitive hematopoietic potential and support the interpretation that these lineages may arise from a common precursor in embryonic life. In addition, they suggest that LIF could play a role in the regulation of primitive erythropoiesis. © 1998 by The American Society of Hematology.

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03-P107 EMT regulated by Wt1 through transcriptional control of Snail-1 and E-cadherin is required for generation of progenitor cells in epicardium and ES cells

Mechanisms of Development ◽

10.1016/j.mod.2009.06.160 ◽

2009 ◽

Vol 126 ◽

pp. S98-S99

Author(s):

Ofelia M. Martínez-Estrada ◽

Laura A. Lettice ◽

Abdelkader Essafi ◽

Juan Antonio Guadix ◽

Joan Slight ◽

...

Keyword(s):

Progenitor Cells ◽

Transcriptional Control ◽

Es Cells ◽

E Cadherin

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Genome-wide screen of promoter methylation analysis of ES cells and ES derived epidermal-like cells

Cell Biochemistry and Function ◽

10.1002/cbf.3129 ◽

2015 ◽

Vol 33 (6) ◽

pp. 398-406 ◽

Cited By ~ 2

Author(s):

Ren-li Zhang ◽

Jin-xiu Meng ◽

Cai-xia Liu ◽

Li-li Zhang ◽

Dong Han ◽

...

Keyword(s):

Promoter Methylation ◽

Es Cells ◽

Methylation Analysis ◽

Genome Wide

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Aquaporin 5 Expression in Mouse Mammary Gland Cells Is Not Driven by Promoter Methylation

BioMed Research International ◽

10.1155/2015/460598 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Barbara Arbeithuber ◽

Roland Thuenauer ◽

Yasmin Gravogl ◽

Zsolt Balogi ◽

Winfried Römer ◽

...

Keyword(s):

Mammary Gland ◽

Tumor Progression ◽

Promoter Methylation ◽

Transcriptional Control ◽

Mouse Mammary Gland ◽

Tissue Type ◽

Mrna Levels ◽

Aquaporin 5 ◽

Aqp5 Expression ◽

And Migration

Several studies have revealed that aquaporins play a role in tumor progression and invasion. In breast carcinomas, high levels of aquaporin 5 (AQP5), a membrane protein involved in water transport, have been linked to increased cell proliferation and migration, thus facilitating tumor progression. Despite the potential role of AQP5 in mammary oncogenesis, the mechanisms controlling mammary AQP5 expression are poorly understood. In other tissues, AQP5 expression has been correlated with its promoter methylation, yet, very little is known about AQP5 promoter methylation in the mammary gland. In this work, we used the mouse mammary gland cell line EpH4, in which we controlled AQP5 expression via the steroid hormone dexamethasone (Dex) to further investigate mechanisms regulating AQP5 expression. In this system, we observed a rapid drop of AQP5 mRNA levels with a delay of several hours in AQP5 protein, suggesting transcriptional control of AQP5 levels. Yet, AQP5 expression was independent of its promoter methylation, or to the presence of negative glucocorticoid receptor elements (nGREs) in its imminent promoter region, but was rather influenced by the cell proliferative state or cell density. We conclude that AQP5 promoter methylation is not a universal mechanism for AQP5 regulation and varies on cell and tissue type.

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KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control

10.1101/522680 ◽

2019 ◽

Author(s):

Navroop K Dhaliwal ◽

Luis E Abatti ◽

Jennifer A Mitchell

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Protein Stability ◽

Rna Polymerase Ii ◽

Half Life ◽

Transcriptional Control ◽

Es Cells ◽

Embryonic Stem ◽

Post Translational Modification ◽

Pluripotent State

AbstractEmbryonic stem (ES) cells are regulated by a network of transcription factors which maintain the pluripotent state. Differentiation relies on downregulation of pluripotency transcription factors disrupting this network. While investigating transcriptional regulation of the pluripotency transcription factor Klf4, we observed homozygous deletion of distal enhancers caused 17 fold decrease in Klf4 transcript but surprisingly decreased protein levels by less than 2 fold indicating post-transcriptional control of KLF4 protein overrides transcriptional control. The lack of sensitivity of KLF4 to transcription is due to high protein stability (half-life >24hr). This stability is context dependent and disrupted during differentiation, evidenced by a shift to a half-life of <2hr. KLF4 protein stability is maintained through interaction with other pluripotency transcription factors (NANOG, SOX2 and STAT3) that together facilitate association of KLF4 with RNA polymerase II. In addition, the KLF4 DNA binding and transactivation domains are required for optimal KLF4 protein stability. Post-translational modification of KLF4 destabilizes the protein as cells exit the pluripotent state and mutations that prevent this destabilization also prevent differentiation. These data indicate the core pluripotency transcription factors are integrated by post-translational mechanisms to maintain the pluripotent state, and identify mutations that increase KLF4 protein stability while maintaining transcription factor function.

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Nutrient-regulated gene expression in eukaryotes

Biochemical Society Symposium ◽

10.1042/bss0730085 ◽

2006 ◽

Vol 73 ◽

pp. 85-96 ◽

Cited By ~ 8

Author(s):

Richard J. Reece ◽

Laila Beynon ◽

Stacey Holden ◽

Amanda D. Hughes ◽

Karine Rébora ◽

...

Keyword(s):

Gene Expression ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcriptional Control ◽

Direct Interaction ◽

Signalling Pathways ◽

A Cell ◽

One Step ◽

Higher Eukaryotes ◽

Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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