Akt1 as a putative regulator of Hox genes

Kong, Kyoung-Ah; Yoon, Hyein; Kim, Myoung Hee

doi:10.1016/j.gene.2012.10.034

Cited by 9 publications

(16 citation statements)

References 36 publications

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“…Unusual expression of Hoxc13 , a deviation from the collinear expression pattern of Hox cluster genes, was found in several tissues at different stages, as has been previously reported 23, 25, 26. Although the mechanisms are not known, Hoxc13 seems to escape the mechanisms regulating the collinear expression of Hoxc genes.…”

Section: Resultssupporting

confidence: 63%

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Hoxc Gene Collinear Expression and Epigenetic Modifications Established during Embryogenesis Are Maintained until after Birth

Min

Lee²,

Kim

2013

Int. J. Biol. Sci.

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The Hox genes, which are organized into clusters on different chromosomes, are key regulators of embryonic anterior-posterior (A-P) body pattern formation and are expressed at specific times and in specific positions in developing vertebrate embryos. Previously, we have shown that histone methylation patterns are closely correlated with collinear Hox gene expression patterns along the A-P axis of E14.5 mouse embryos. Since histone modification is thought to play a crucial mechanistic role in the highly coordinated pattern of collinear Hox gene expression, we examined the maintenance of the spatial collinear expression pattern of Hoxc genes and the corresponding histone modifications during embryogenesis and in early postnatal mice. Hox expression patterns and histone modifications were analyzed by semi-quantitative RT-PCR and chromatin immunoprecipitation (ChIP)-PCR analyses, respectively. The spatiotemporal expression patterns of Hoxc genes in a cluster were maintained until the early postnatal stage (from E8.5 through P5). Examination of histone modifications in E14.5 and P5 tissues revealed that level of H3K27me3 is only a weak correlation with collinear Hoxc gene expression in the trunk regions although diminished in general, however the enrichment of H3K4me3 is strongly correlated with the gene expression in both stages. In summary, the initial spatiotemporal collinear expression pattern of Hoxc genes and epigenetic modifications are maintained after birth, likely contributing to the establishment of the gene expression code for position in the anatomic body axis throughout the entire life of the organism.

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Section: Resultssupporting

confidence: 63%

“…PCR amplification was performed under the following conditions: initial denaturation for 5 minutes at 95°C, and then 32 cycles of 95°C for 30 seconds, 58°C for 30 seconds, and 72°C for 30 seconds. The PCR primer sequences used were as previously described 21, 23.…”

Section: Methodsmentioning

confidence: 99%

Hoxc Gene Collinear Expression and Epigenetic Modifications Established during Embryogenesis Are Maintained until after Birth

Min

Lee²,

Kim

2013

Int. J. Biol. Sci.

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“…Specifically, only the C12|11 site exhibited a differential DNA methylation pattern between the two MEF cell lines, which likely led to differential CTCF binding at this site. Akt1 has been reported to be involved in DNA methylation by regulating DNA methyltransferase stability through phosphorylation of DNMT1 and increasing transcript levels of DNMT3b , although it is not clear whether this was the case at C12|11 CSE sites in our study. In Akt1 −/− MEFs, CpG hypomethylation at CTCF binding sites between Hoxc11 and ‐ c12 genes (C12|11) likely increased CTCF binding affinity in the Hoxc11 upstream region and induced concomitant cell type‐specific DNA loop formation and posterior Hoxc gene expression as well.…”

Section: Resultscontrasting

confidence: 61%

CTCF‐mediated Chromatin Loop for the Posterior Hoxc Gene Expression in MEF Cells

et al. 2016

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Modulation of chromatin structure has been proposed as a molecular mechanism underlying the spatiotemporal collinear expression of Hox genes during development. CCCTC-binding factor (CTCF)-mediated chromatin organization is now recognized as a crucial epigenetic mechanism for transcriptional regulation. Thus, we examined whether CTCF-mediated chromosomal conformation is involved in Hoxc gene expression by comparing wild-type mouse embryonic fibroblast (MEF) cells expressing anterior Hoxc genes with Akt1 null MEFs expressing anterior as well as posterior Hoxc genes. We found that CTCF binding between Hoxc11 and -c12 is important for CTCF-mediated chromosomal loop formation and concomitant posterior Hoxc gene expression. Hypomethylation at this site increased CTCF binding and recapitulated the chromosomal conformation and posterior Hoxc gene expression patterns observed in Akt1 null MEFs. From this work we found that CTCF at the C12|11 does not function as a barrier/boundary, instead let the posterior Hoxc genes switch their interaction from inactive centromeric to active telomeric genomic niche, and concomitant posterior Hoxc gene expression. Although it is not clear whether CTCF affects Hoxc gene expression solely through its looping activity, CTCF-mediated chromatin structural modulation could be an another tier of Hox gene regulation during development. V C 2016 IUBMB Life, 68(6): [436][437][438][439][440][441][442][443][444] 2016

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“…Furthermore, we recently identified, for the first time, that Akt1 negatively regulates several posterior 5′ Hoxc cluster genes through epigenetic modification in mouse embryonic fibroblasts isolated from mouse embryonic day 14.5 (E14.5) (Kong et al . , ). Since E14.5 MEF cells represent a later developmental stage (late gastrula), by the time collinear expression of Hox genes is established, the maintenance mechanism for collinear expression of Hox genes must have been initiated.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in our previous study, we identified Akt1 as a novel putative regulator of 5′ Hoxc genes in mouse embryonic fibroblast (MEF) cells (Kong et al . ). Although, both the RA and PI3K/Akt pathway play critical roles in regulating Hox gene expression and cell differentiation, there is no evidence indicating that RA‐induced Hox gene expression occurs through the PI3K/Akt signaling pathway.…”

Section: Introductionmentioning

confidence: 97%

PI3K/Akt pathway regulates retinoic acid‐induced Hox gene expression in F9 cells

Lee

Kim

2014

Dev Growth Differ

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Retinoic acid (RA), the most potent natural form of vitamin A, is a key morphogen in vertebrate development and a potent regulator of both adult and embryonic cell differentiation. Specifically, RA regulates clustered Hox gene expression during embryogenesis and is required to establish the anteroposterior body plan. The PI3K/Akt pathway was also reported to play an essential role in the process of RA-induced cell differentiation. Therefore, we tested whether the PI3K/Akt pathway is involved in RA-induced Hox gene expression in a F9 murine embryonic teratocarcinoma cells. To examine the effect of PI3K/Akt signaling on RA-induced initiation of collinear expression of Hox genes, F9 cells were treated with RA in the presence or absence of PI3K inhibitor LY294002, and time-course gene expression profiles for all 39 Hox genes located in four different clustersHoxa, Hoxb, Hoxc, and Hoxd-were analyzed. Collinear expression of Hoxa and -b cluster genes was initiated earlier than that of the -c and -d clusters upon RA treatment. When LY294002 was applied along with RA, collinear expression induced by RA was delayed, suggesting that the PI3K/Akt signaling pathway somehow regulates RA-induced collinear expression of Hox genes in F9 cells. The initiation of Hox collinear expression by RA and the delayed expression following LY294002 in F9 cells would provide a good model system to decipher the yet to be answered de novo collinear expression of Hox genes during gastrulation, which make the gastrulating cells to remember their positional address along the AP body axis in the developing embryo.

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Akt1 as a putative regulator of Hox genes

Cited by 9 publications

References 36 publications

Hoxc Gene Collinear Expression and Epigenetic Modifications Established during Embryogenesis Are Maintained until after Birth

Hoxc Gene Collinear Expression and Epigenetic Modifications Established during Embryogenesis Are Maintained until after Birth

CTCF‐mediated Chromatin Loop for the Posterior Hoxc Gene Expression in MEF Cells

PI3K/Akt pathway regulates retinoic acid‐induced Hox gene expression in F9 cells

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