Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170389 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transforming growth factor-b (TGF-b) regulates various aspects of vascular development, yet the signaling mechanisms of TGF-b in the control of angiogenesis remain poorly characterized. Here we show that homeodomain interacting protein kinases, HIPK1 and HIPK2, are transcriptional corepressors that regulate TGF-b-depednent angiogenesis during embryonic development. Loss of HIPK1 and HIPK2 leads to marked up-regulations of several potent angiogenic genes, including Vegf and Mmp10, which result in excessive endothelial proliferation and poor adherens junction formation. This robust phenotype can be recapitulated by siRNA knock down of Hipk1 and Hipk2 in human umbilical vein endothelial cells, as well as in endothelial cell-specific TGF-b type II receptor (TbRII) conditional mutants. The effects of HIPK proteins are mediated through its interaction with MEF2C and HDAC7, and this interaction can be further enhanced by TGF-b and TAK1. Remarkably, TGF-b-TAK1 signaling activates HIPK2 by phosphorylating a highly conserved tyrosine residue Y-361 within the kinase domain. Point mutation in this tyrosine completely eliminates the effect of HIPK2 in the transcriptional suppression of target genes. Together, these results reveal a previously unrecognized role of HIPK proteins in connecting TGF-b signaling pathway with the transcriptional programs for angiogenesis in early embryonic development. In this study, a total of 36,000 transcripts and ESTs (a total of 30,000 unique genes) was used to acquire expression profiles among the control, Hipk1-/-, Hipk2-/-, and Hipk1-/-;Hipk2-/- E9.5 embryos. This will allow us unsupervised and successfully to analyze the transcriptomes and finally to reveal the role of HIPK1 and HIPK2 in the signal transduction mechanism downstream of TGF-b and the transcriptional control of angiogenic gene expression during the critical stages of vascular morphogenesis.
2013-06-01 | E-GEOD-39253 | biostudies-arrayexpress
Project description:Transforming growth factor-b (TGF-b) regulates various aspects of vascular development, yet the signaling mechanisms of TGF-b in the control of angiogenesis remain poorly characterized. Here we show that homeodomain interacting protein kinases, HIPK1 and HIPK2, are transcriptional corepressors that regulate TGF-b-depednent angiogenesis during embryonic development. Loss of HIPK1 and HIPK2 leads to marked up-regulations of several potent angiogenic genes, including Vegf and Mmp10, which result in excessive endothelial proliferation and poor adherens junction formation. This robust phenotype can be recapitulated by siRNA knock down of Hipk1 and Hipk2 in human umbilical vein endothelial cells, as well as in endothelial cell-specific TGF-b type II receptor (TbRII) conditional mutants. The effects of HIPK proteins are mediated through its interaction with MEF2C and HDAC7, and this interaction can be further enhanced by TGF-b and TAK1. Remarkably, TGF-b-TAK1 signaling activates HIPK2 by phosphorylating a highly conserved tyrosine residue Y-361 within the kinase domain. Point mutation in this tyrosine completely eliminates the effect of HIPK2 in the transcriptional suppression of target genes. Together, these results reveal a previously unrecognized role of HIPK proteins in connecting TGF-b signaling pathway with the transcriptional programs for angiogenesis in early embryonic development.
2013-06-01 | GSE39253 | GEO
Project description:Expression profiling of fetal liver erythroid precursors after either Hipk1 or Hipk2 knockdown by shRNA versus control shRNA Two condition experiment, Hipk1 or Hipk2 knockdown versus control (shRNA against luciferase), two replicates each shRNA
2010-05-16 | E-GEOD-17106 | biostudies-arrayexpress
Project description:Expression profiling of fetal liver erythroid precursors after either Hipk1 or Hipk2 knockdown by shRNA versus control shRNA
2009-07-16 | GSE17106 | GEO
Project description:Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins). Abstract (submitted paper): rationale for expression profiling Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentâbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationâexplained in part by impaired cell cycle progression as well as increased apoptosisâand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesisâsuch as alpha-globin and mitoferrin 1âdemonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.
2010-07-08 | E-GEOD-20391 | biostudies-arrayexpress
Project description:TGF-beta signaling in neural crest cells is required for normal craniofacial development. This signaling can be transduced via TGF-beta type I receptors (TGFbRI) using Smad-dependent or Smad independent signaling pathways. We used microarrays to identify TGF-beta-responsive genes that are dependent either on TGFbRI kinase, Tak1 kinase or both. Primary palatal mesenchymal cell cultures were established. Cultured cells were stimulated with TGF-beta2 in the presence or absence of TGFbRI kinase and Tak1 kinase inhibitors. Unstimulated cells were used as controls. Total RNAs were isolated and hybridized on Affymetrix microarrays.
2013-03-27 | E-GEOD-45491 | biostudies-arrayexpress
Project description:Murine fetal liver TER119-negative erythroid precursors: Hipk1 or Hipk2 knockdown versus control
| PRJNA119787 | ENA
Project description:HIPK2, a member of the homeodomain-interacting protein kinase family, is a transcriptional corepressor whose activity inhibits tumor progression and allows tumor cell apoptosis in response to chemotherapy. HIPK2 regulates the function of numerous molecules and its inhibition by siRNA, hypoxia or mutations, strongly favours molecular pathways involved in tumor progression, angiogenesis, invasion and chemoresistance. Hence the identification of novel molecules regulated by HIPK2 may be beneficial for better understanding tumor progression and for evaluating targeted antitumor therapies. By using microarray analysis, derived from HIPK2 overexpression (that mimics HIPK2 activation) in colon cancer RKO cells, we aim at evaluating the HIPK2 modulated gene expression involved in tumor progression.
2011-12-31 | E-GEOD-31089 | biostudies-arrayexpress
Project description:HIPK2, a member of the homeodomain-interacting protein kinase family, is a transcriptional corepressor whose activity inhibits tumor progression and allows tumor cell apoptosis in response to chemotherapy. HIPK2 regulates the function of numerous molecules and its inhibition by siRNA, hypoxia or mutations, strongly favours molecular pathways involved in tumor progression, angiogenesis, invasion and chemoresistance. Hence the identification of novel molecules regulated by HIPK2 may be beneficial for better understanding tumor progression and for evaluating targeted antitumor therapies.
2011-12-31 | GSE31089 | GEO
Project description:TGF-beta signaling in neural crest cells is required for normal craniofacial development. This signaling can be transduced via TGF-beta type I receptors (TGFbRI) using Smad-dependent or Smad independent signaling pathways. We used microarrays to identify TGF-beta-responsive genes that are dependent either on TGFbRI kinase, Tak1 kinase or both.
2013-03-27 | GSE45491 | GEO