Pdgfr{alpha} and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells

Lloyd A Pereira; Michael Wong; Anna K Mossman; Koula Sourris; Mary E Janes; Kathy Knezevic; Claire Elizabeth Hirst; Sue Mei Lim; John E Pimanda; Edouard G Stanley; Andrew G Elefanty

doi:10.1016/j.scr.2011.09.007

Pdgfr{alpha} and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells

Lloyd A Pereira, Michael Wong, Anna K Mossman, Koula Sourris, Mary E Janes, Kathy Knezevic, Claire Elizabeth Hirst, Sue Mei Lim, John E Pimanda, Edouard G Stanley, Andrew G Elefanty

Research output: Contribution to journal › Article › Research › peer-review

17 Citations (Scopus)

Abstract

The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hygro) mouse embryonic stem cells to identify potential downstream transcriptional targets of Mixl1. Candidate Mixl1 regulated genes whose expression was reduced in GFP+ cells isolated from differentiating Mixl1(GFP/Hygro) embryoid bodies included Pdgfralpha and Flk1. Mixl1 bound to ATTA sequences located in the Pdgfralpha and Flk1 promoters and chromatin immunoprecipitation assays confirmed Mixl1 occupancy of these promoters in vivo. Furthermore, Mixl1 transactivated the Pdgfralpha and Flk1 promoters through ATTA sequences in a DNA binding dependent manner. These data support the hypothesis that Mixl1 directly regulates Pdgfralpha and Flk1 gene expression and strengthens the position of Mixl1 as a key regulator of mesendoderm development during mammalian gastrulation.

Original language	English
Pages (from-to)	165 - 179
Number of pages	15
Journal	Stem Cell Research
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.scr.2011.09.007
Publication status	Published - 2012

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title = "Pdgfr{alpha} and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells",

abstract = "The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hygro) mouse embryonic stem cells to identify potential downstream transcriptional targets of Mixl1. Candidate Mixl1 regulated genes whose expression was reduced in GFP+ cells isolated from differentiating Mixl1(GFP/Hygro) embryoid bodies included Pdgfralpha and Flk1. Mixl1 bound to ATTA sequences located in the Pdgfralpha and Flk1 promoters and chromatin immunoprecipitation assays confirmed Mixl1 occupancy of these promoters in vivo. Furthermore, Mixl1 transactivated the Pdgfralpha and Flk1 promoters through ATTA sequences in a DNA binding dependent manner. These data support the hypothesis that Mixl1 directly regulates Pdgfralpha and Flk1 gene expression and strengthens the position of Mixl1 as a key regulator of mesendoderm development during mammalian gastrulation.",

author = "Pereira, {Lloyd A} and Michael Wong and Mossman, {Anna K} and Koula Sourris and Janes, {Mary E} and Kathy Knezevic and Hirst, {Claire Elizabeth} and Lim, {Sue Mei} and Pimanda, {John E} and Stanley, {Edouard G} and Elefanty, {Andrew G}",

year = "2012",

doi = "10.1016/j.scr.2011.09.007",

language = "English",

volume = "8",

pages = "165 -- 179",

journal = "Stem Cell Research",

issn = "1873-5061",

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T1 - Pdgfr{alpha} and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells

AU - Pereira, Lloyd A

AU - Wong, Michael

AU - Mossman, Anna K

AU - Sourris, Koula

AU - Janes, Mary E

AU - Knezevic, Kathy

AU - Hirst, Claire Elizabeth

AU - Lim, Sue Mei

AU - Pimanda, John E

AU - Stanley, Edouard G

AU - Elefanty, Andrew G

PY - 2012

Y1 - 2012

N2 - The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hygro) mouse embryonic stem cells to identify potential downstream transcriptional targets of Mixl1. Candidate Mixl1 regulated genes whose expression was reduced in GFP+ cells isolated from differentiating Mixl1(GFP/Hygro) embryoid bodies included Pdgfralpha and Flk1. Mixl1 bound to ATTA sequences located in the Pdgfralpha and Flk1 promoters and chromatin immunoprecipitation assays confirmed Mixl1 occupancy of these promoters in vivo. Furthermore, Mixl1 transactivated the Pdgfralpha and Flk1 promoters through ATTA sequences in a DNA binding dependent manner. These data support the hypothesis that Mixl1 directly regulates Pdgfralpha and Flk1 gene expression and strengthens the position of Mixl1 as a key regulator of mesendoderm development during mammalian gastrulation.

AB - The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hygro) mouse embryonic stem cells to identify potential downstream transcriptional targets of Mixl1. Candidate Mixl1 regulated genes whose expression was reduced in GFP+ cells isolated from differentiating Mixl1(GFP/Hygro) embryoid bodies included Pdgfralpha and Flk1. Mixl1 bound to ATTA sequences located in the Pdgfralpha and Flk1 promoters and chromatin immunoprecipitation assays confirmed Mixl1 occupancy of these promoters in vivo. Furthermore, Mixl1 transactivated the Pdgfralpha and Flk1 promoters through ATTA sequences in a DNA binding dependent manner. These data support the hypothesis that Mixl1 directly regulates Pdgfralpha and Flk1 gene expression and strengthens the position of Mixl1 as a key regulator of mesendoderm development during mammalian gastrulation.

UR - http://www.sciencedirect.com/science/article/pii/S1873506111001218

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DO - 10.1016/j.scr.2011.09.007

M3 - Article

SN - 1873-5061

VL - 8

SP - 165

EP - 179

JO - Stem Cell Research

JF - Stem Cell Research

IS - 2

ER -

Pdgfr{alpha} and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells

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