Jarid1b targets genes regulating development and is involved in neural differentiation [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31966 | GEO | 2011/10/27
SECONDARY ACCESSION(S): PRJNA155275
REPOSITORIES: GEO
Similar Datasets
Project description:We analyzed the genome-wide binding profile of Jarid1b in mouse ESCs. We find that Jarid1b localizes mainly to transcription start sites, of which more than 50% are also bound by Polycomb proteins and are enriched for genes encoding developmental regulators. Furthermore, we generated genome-wide mapping of H3K4me3 in LKO Scramble and LKO Jarid1b mouse ESCs. Virtually all Jarid1b binding sites are positive for H3K4me3. Upon knockdown of Jarid1b, H3K4me3 is significantly increased at Jarid1b positive regions. Examination of Jarid1b and H3K4me3 in mouse ES cells
2011-10-26 | E-GEOD-31966 | biostudies-arrayexpress
Project description:Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. * Lack of Jarid1b leads to major neonatal lethality and defects in neural systems * Jarid1b mutants display homeotic skeletal transformations * H3K4me3 is increased at inactive transcriptional regulators in Jarid1b-/- embryos * Chromatin changes are accompanied by elevated levels of key neural transcription factors
2013-04-26 | GSE41171 | GEO
Project description:Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. * Lack of Jarid1b leads to major neonatal lethality and defects in neural systems * Jarid1b mutants display homeotic skeletal transformations * H3K4me3 is increased at inactive transcriptional regulators in Jarid1b-/- embryos * Chromatin changes are accompanied by elevated levels of key neural transcription factors
2013-04-26 | GSE41172 | GEO
Project description:Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. * Lack of Jarid1b leads to major neonatal lethality and defects in neural systems * Jarid1b mutants display homeotic skeletal transformations * H3K4me3 is increased at inactive transcriptional regulators in Jarid1b-/- embryos * Chromatin changes are accompanied by elevated levels of key neural transcription factors Determining H3K4me3 and H3K27me3 in early (E8.5) mouse embryos
2013-04-26 | E-GEOD-41172 | biostudies-arrayexpress
Project description:Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. * Lack of Jarid1b leads to major neonatal lethality and defects in neural systems * Jarid1b mutants display homeotic skeletal transformations * H3K4me3 is increased at inactive transcriptional regulators in Jarid1b-/- embryos * Chromatin changes are accompanied by elevated levels of key neural transcription factors RNA was extracted from heads of E8.5 embryos, three pools of 4 heads each were used per genotype
2013-04-26 | E-GEOD-41171 | biostudies-arrayexpress
Project description:The H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for embryonic stem cell (ESC) self-renewal, but essential for ESC differentiation along the neural lineage. During neural differentiation, Jarid1b depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation.
2011-10-27 | GSE31967 | GEO
Project description:The H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for embryonic stem cell (ESC) self-renewal, but essential for ESC differentiation along the neural lineage. During neural differentiation, Jarid1b depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation. Control (LKOScr) or Jarid1b knockdown (LKOJarid1b) mouse ES cells were used.Each experiment was performed in triplicates.
2011-10-26 | E-GEOD-31967 | biostudies-arrayexpress
Project description:The jmjC-domain containing H3K4 histone demethylase JARID1B/KDM5B/PLU1 is over-expressed in human breast cancer and is a potential target for breast cancer treatment. To investigate the in vivo function of JARID1B, we developed a new strain of Jarid1b knockout mice and characterized the phenotypes in detail. Unlike previously reported knockout strains, the majority of our Jarid1b knockout mice are viable beyond embryonic and neonatal stages. Nonetheless, these mice exhibit decreased body weight, higher incidence of adult mortality and decreased female fertility. Furthermore, Jarid1b knockout mice show delayed mammary gland development. Mechanistically, loss of JARID1B leads to decreased serum estrogen levels and reduced proliferation of mammary epithelial cells in early puberty. In addition, in mammary epithelial cells, loss of JARID1B diminishes the expression of key regulators of mammary morphogenesis, including FOXA1, estrogen receptor α (ERα), and GATA3. Taken together, these results indicate that JARID1B positively regulates mammary ductal development through both extrinsic and cell-autonomous mechanisms.
2014-05-19 | GSE50479 | GEO
Project description:Recurrent mutations in histone modifying enzymes in multiple cancer types imply key roles in tumorigenesis. However, the functional relevance of these mutations remains unknown. Here we show that the JARID1B histone H3 lysine 4 demethylase is frequently amplified and overexpressed in luminal breast tumors and a somatic point mutation of JARID1B leads to the gain of luminal-specific gene expression programs. Downregulation of JARID1B in luminal breast cancer cells induces the expression of basal cell-specific genes and growth arrest, which is partially rescued by the inhibition of TGFBR thereby indicating a key role for TGFb signaling. Integrated genome-wide analysis of JARID1B chromatin binding, histone H3 lysine trimethyl (H3K4me3) and dimethyl (H3K4me2) patterns, and gene expression profiles in luminal and basal-like breast cancer cells suggest a key role for JARID1B in luminal cell-specific gene expression programs. A significant fraction of JARID1B binding-sites overlaps with CTCF in both luminal and basal-like breast cancer cells. CTCF also co-immunoprecipitates with JARID1B and it may influence its histone demethylase (HDM) activity as the H3K4me3/me2 ratio is lower at the CTCF-overlapping compared to JARID1B-unique sites. Additionally, a heterozygous JARID1B missense mutation (K1435R) in the HCC2157 basal-like breast cancer cell line is associated with unique JARID1B chromatin-binding and gene expression patterns implying gain of luminal features. In line with this, exogenous expression of this mutant in basal-like breast cancer cells leads to a gain of JARID1B binding at many luminal-specific genes. A PARADIGM score reflecting JARID1B activity in luminal breast cancer cells is associated with poor clinical outcome in patients with luminal breast tumors. Together, our data imply that JARID1B is a luminal lineage-driving oncogene and that its therapeutic targeting may represent a novel therapeutic strategy in treatment-resistant luminal breast tumors. ChIP-Seq on JARID1B, H3K4me2, H3K4me3, CTFC, and input on breast cancer cell-lines. 50 cycles of sequencing on Illumina platform in 6 cell-lines.
2014-06-17 | E-GEOD-46055 | biostudies-arrayexpress
Project description:Recurrent mutations in histone modifying enzymes in multiple cancer types imply key roles in tumorigenesis. However, the functional relevance of these mutations remains unknown. Here we show that the JARID1B histone H3 lysine 4 demethylase is frequently amplified and overexpressed in luminal breast tumors and a somatic point mutation of JARID1B leads to the gain of luminal-specific gene expression programs. Downregulation of JARID1B in luminal breast cancer cells induces the expression of basal cell-specific genes and growth arrest, which is partially rescued by the inhibition of TGFBR thereby indicating a key role for TGFb signaling. Integrated genome-wide analysis of JARID1B chromatin binding, histone H3 lysine trimethyl (H3K4me3) and dimethyl (H3K4me2) patterns, and gene expression profiles in luminal and basal-like breast cancer cells suggest a key role for JARID1B in luminal cell-specific gene expression programs. A significant fraction of JARID1B binding-sites overlaps with CTCF in both luminal and basal-like breast cancer cells. CTCF also co-immunoprecipitates with JARID1B and it may influence its histone demethylase (HDM) activity as the H3K4me3/me2 ratio is lower at the CTCF-overlapping compared to JARID1B-unique sites. Additionally, a heterozygous JARID1B missense mutation (K1435R) in the HCC2157 basal-like breast cancer cell line is associated with unique JARID1B chromatin-binding and gene expression patterns implying gain of luminal features. In line with this, exogenous expression of this mutant in basal-like breast cancer cells leads to a gain of JARID1B binding at many luminal-specific genes. A PARADIGM score reflecting JARID1B activity in luminal breast cancer cells is associated with poor clinical outcome in patients with luminal breast tumors. Together, our data imply that JARID1B is a luminal lineage-driving oncogene and that its therapeutic targeting may represent a novel therapeutic strategy in treatment-resistant luminal breast tumors.
2014-06-17 | GSE49794 | GEO