Developmental changes in DNA methylation and covalent histone modifications of chromatin associated with the ε-, γ-, and β-globin gene promoters in Papio anubis

Lavelle, Donald; Vaitkus, Kestis; Hankewych, Maria; Singh, Mahipal; DeSimone, Joseph

doi:10.1016/j.bcmd.2006.01.004

Cited by 22 publications

(22 citation statements)

References 42 publications

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“…33,34 The 2 groups reported that the levels of histone H3 acetylation at the globin promoters were correlated to gene activation (ie, the ␥ gene promoter was heavily acetylated at the fetal stage of development, a low level of acetylation was measured at the ␤ gene promoter, and a reciprocal correlation was observed in adult erythroid cells). Our results demonstrate that excellent correlation between gene activation and hyperacetylation occurs only in the exon regions.…”

Section: Discussionmentioning

confidence: 99%

Histone acetylation at the human β-globin locus changes with developmental age

Yin

Barkess

Fang

et al. 2007

Blood

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To delineate the relationship between epigenetic modifications and hemoglobin switching, we compared the pattern of histone acetylation and pol II binding across the ␤-globin locus at fetal and adult stages of human development. To make this comparison possible, we introduced an external control into experimental samples in chromatin immunoprecipitation (ChIP) assays. Using this common standard, we found that the locus control region (LCR) was acetylated to the same level at all stages, whereas acetylation levels at the individual gene regions correlated with the state of transcription. In the active genes, the promoters were less acetylated compared with the coding regions. Furthermore, all globin promoters were acetylated to a similar level irrespective of the state of transcription. However, after correction for the loss of nucleosomes, the level of acetylation per histone at the active ␥ and ␤ promoters was 5-to 7-fold greater than that at the inactive promoter. Although the histone acetylation level within the LCR was developmentally stable, pol II binding in fetal erythroblasts was 2-to 3-fold greater than that in adult erythroblasts. These results demonstrate that dynamic changes in histone acetylation and pol II take place as the human ␤-globin gene region undergoes its developmental switches. IntroductionThe human ␤-globin locus consists of around 100 kb found on chromosome 11 and is composed of 5 functional genes: ε, G ␥, A ␥, ␦, and ␤, which are arranged in the order of their expression during development. The locus also contains a locus control region (LCR) that consists of 5 DNase I hypersensitive sites (HS). The LCR is essential for physiologic level expression in mice, although it is not required for chromatin opening activities. 1,2 The tissue-specific expression of the embryonic, fetal, and adult globin genes is developmentally regulated and the globin genes undergo 2 switches in expression during development. The ε-globin gene is expressed in embryonic development at the blood island of the yolk sac. At approximately 6 to 8 weeks of gestation, ε-globin is silenced, whereas the G ␥-and A ␥-globin genes are activated in the fetal liver. The second switch occurs late in gestation when the fetal ␥-globin genes are progressively silenced, although ␤-globin is eventually expressed at high levels after birth. 3 The exact mechanism by which these complex switches occur is not yet fully understood.Chromatin epigenetic changes have long been thought to play a role in the expression of genes. 4,5 With regard to the core histones, the effects of covalent modifications are 2-fold. First, modifications such as acetylation, methylation, and phosphorylation help change the access of trans-acting factors to the genetic elements found within the chromatin and affect the binding specificity of certain trans-factors. 6 Second, these modifications can affect the physical property of chromatin, such as compactness, stability, and flexibility. [7][8][9] Generally, histone acetylation makes the chromatin more flexibl...

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Section: Discussionmentioning

confidence: 99%

Histone acetylation at the human β-globin locus changes with developmental age

Yin

Barkess

Fang

et al. 2007

Blood

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“…Chromatin immunoprecipitation analysis was performed as previously described 39 with modifications (Online Supplementary Appendix).…”

Section: Chromatin Immunoprecipitation Analysismentioning

confidence: 99%

The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis)

et al. 2016

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“…Because of numerous studies showing it associated with heterochromatin, DNA methylation has gained a reputation as a permanent, silencing mark (Jaenisch 1997;Walsh et al 1998;Bird and Wolffe 1999;Siegfried et al 1999;Fuks et al 2003;Hashimshony et al 2003;Zhang et al 2005;Reik 2007;Esteller 2008;Tiwari et al 2008). However, recently, regions of methylated DNA have been correlated with the tissue-specific expression of several genes and with active coding regions across the genome (Kumar and Biswas 1988;Ngo et al 1996;Grunau et al 2000;Imamura et al 2001;Kroft et al 2001;Kusui et al 2001;Futscher et al 2002;Song et al 2005;Butta et al 2006;Da et al 2006;Fujii et al 2006;Lavelle et al 2006;Douet et al 2007;Hellman and Chess 2007;Kitamura et al 2007;Shen et al 2007;Zilberman et al 2007;Yagi et al 2008). Additionally, rather than a permanent mark, methylation has been shown to be dynamic, capable of temporally changing at gene promoters (Weiss and Cedar 1997;Kangaspeska et al 2008;Metivier et al 2008).…”

Section: San Diego California 92121 Usamentioning

confidence: 99%

Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver

Brunner¹,

Johnson²,

Kim³

et al. 2009

Genome Res.

261

218

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To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivatives, and human tissues allowed us to identify several trends during hESC and in vivo liver differentiation. First, differentiation results in DNA methylation changes at a minimal number of assayed regions, both in vitro and in vivo (2%-11%). Second, in vitro hESC differentiation is characterized by both de novo methylation and demethylation, whereas in vivo fetal liver development is characterized predominantly by demethylation. Third, hESC differentiation is uniquely characterized by methylation changes specifically at H3K27me3-occupied regions, bivalent domains, and low density CpG promoters (LCPs), suggesting that these regions are more likely to be involved in transcriptional regulation during hESC differentiation. Although both H3K27me3-occupied domains and LCPs are also regions of high variability in DNA methylation state during human liver development, these regions become highly unmethylated, which is a distinct trend from that observed in hESCs. Taken together, our results indicate that hESC differentiation has a unique DNA methylation signature that may not be indicative of in vivo differentiation.

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Developmental changes in DNA methylation and covalent histone modifications of chromatin associated with the ε-, γ-, and β-globin gene promoters in Papio anubis

Cited by 22 publications

References 42 publications

Histone acetylation at the human β-globin locus changes with developmental age

Histone acetylation at the human β-globin locus changes with developmental age

The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis)

Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver

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