Title:
Reduction of Hox gene expression by H1 depletion

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dc.contributor.author Zhang, Yunzhe en_US
dc.contributor.author Liu, Zheng en_US
dc.contributor.author Medrzycki, Magdalena en_US
dc.contributor.author Cao, Kaixiang en_US
dc.contributor.author Fan, Yuhong en_US
dc.contributor.corporatename Georgia Institute of Technology. School of Biology en_US
dc.contributor.corporatename Georgia Institute of Technology. Institute for Bioengineering and Bioscience en_US
dc.date.accessioned 2013-08-23T19:15:20Z
dc.date.available 2013-08-23T19:15:20Z
dc.date.issued 2012-06-11
dc.description © 2012 Zhang et al. 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. en_US
dc.description DOI: 10.1371/journal.pone.0038829 en_US
dc.description.abstract The evolutionarily conserved homeotic (Hox) genes are organized in clusters and expressed collinearly to specify body patterning during embryonic development. Chromatin reorganization and decompaction are intimately connected with Hox gene activation. Linker histone H1 plays a key role in facilitating folding of higher order chromatin structure. Previous studies have shown that deletion of three somatic H1 subtypes together leads to embryonic lethality and that H1c/H1d/H1e triple knockout (TKO) embryonic stem cells (ESCs) display bulk chromatin decompaction. To investigate the potential role of H1 and higher order chromatin folding in the regulation of Hox gene expression, we systematically analyzed the expression of all 39 Hox genes in triple H1 null mouse embryos and ESCs by quantitative RT-PCR. Surprisingly, we find that H1 depletion causes significant reduction in the expression of a broad range of Hox genes in embryos and ESCs. To examine if any of the three H1 subtypes (H1c, H1d and H1e) is responsible for decreased expression of Hox gene in triple-H1 null ESCs, we derived and characterized H1c2/2, H1d2/2, and H1e2/2 single-H1 null ESCs. We show that deletion of individual H1 subtypes results in down-regulation of specific Hox genes in ESCs. Finally we demonstrate that, in triple-H1- and single-H1- null ESCs, the levels of H3K4 trimethylation (H3K4me3) and H3K27 trimethylation (H3K27me3) were affected at specific Hox genes with decreased expression. Our data demonstrate that marked reduction in total H1 levels causes significant reduction in both expression and the level of active histone mark H3K4me3 at many Hox genes and that individual H1 subtypes may also contribute to the regulation of specific Hox gene expression. We suggest possible mechanisms for such an unexpected role of histone H1 in Hox gene regulation. en_US
dc.identifier.citation Zhang Y., Liu Z., Medrzycki M., Cao K., Fan Y. (2012) Reduction of Hox Gene Expression by Histone H1 Depletion. PLoS ONE 7(6): e38829 en_US
dc.identifier.doi 10.1371/journal.pone.0038829
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/1853/48728
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.publisher.original Public Library of Science
dc.subject Hox genes en_US
dc.subject Body patterning en_US
dc.subject Embryonic development en_US
dc.subject Embryonic stem cells en_US
dc.subject ESCs en_US
dc.subject Histone H1 depletion en_US
dc.title Reduction of Hox gene expression by H1 depletion en_US
dc.type Text
dc.type.genre Article
dspace.entity.type Publication
local.contributor.author Fan, Yuhong
local.contributor.corporatename College of Sciences
local.contributor.corporatename School of Biological Sciences
relation.isAuthorOfPublication 8a6f8119-7916-40bb-8d71-f6c244209e45
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
relation.isOrgUnitOfPublication c8b3bd08-9989-40d3-afe3-e0ad8d5c72b5
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