The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3
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...
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creator | Albert, Mareike Schmitz, Sandra U Kooistra, Susanne M Malatesta, Martina Morales Torres, Cristina Rekling, Jens C Johansen, Jens V Abarrategui, Iratxe Helin, Kristian |
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 target genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants, supporting a functional interplay between Polycomb proteins and Jarid1b. To understand how Jarid1b regulates mouse development, we performed a genome-wide analysis of histone modifications, which demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 during early embryogenesis in Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators like Pax6 and Otx2 in Jarid1b knockout brains. Taken together, these results suggest that Jarid1b regulates mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. |
doi_str_mv | 10.1371/journal.pgen.1003461 |
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Albert M, Schmitz SU, Kooistra SM, Malatesta M, Morales Torres C, et al. (2013) The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3. 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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 target genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants, supporting a functional interplay between Polycomb proteins and Jarid1b. To understand how Jarid1b regulates mouse development, we performed a genome-wide analysis of histone modifications, which demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 during early embryogenesis in Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators like Pax6 and Otx2 in Jarid1b knockout brains. Taken together, these results suggest that Jarid1b regulates mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23637629</pmid><doi>10.1371/journal.pgen.1003461</doi><oa>free_for_read</oa></addata></record> |
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subjects | Acquisitions & mergers Animals Binding sites Biology Chromatin Defects Embryonic Development Gene expression Genes, Developmental Genetic aspects Genetics Genomes Health aspects Histones Histones - metabolism Insects Jumonji Domain-Containing Histone Demethylases - genetics Mice Nuclear Proteins - genetics Physiological aspects Polycomb-Group Proteins - genetics Proteins Repressor Proteins - genetics Rodents Stem cells Studies Transcription factors |
title | The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3 |
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