The inactivation of the π gene in chicken erythroblasts of adult lineage is not mediated by packaging of the embryonic part of the α-globin gene domain into a repressive heterochromatin-like structure

Ioudinkova, E. S.; Ulianov, Sergey V.; Bunina, Daria; Iarovaia, Olga V.; Гаврилов, А. В.; Razin, Sergey V.

doi:10.4161/epi.6.12.18215

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…S3), and this observation is in agreement with the data published by others. 21 Instead, we observed a constant incorporation of active histone marks like H3ac, H4ac, and H3K4me2 (Fig. 4B).…”

Section: Resultsmentioning

confidence: 77%

“…This is in agreement with the previously proposed role of the α D promoter region as a constitutive anchor point for the α-globin domain chromatin hub. 17,21 In conclusion, even though the locus is in a general open chromatin conformation there is a preference for the 3' enhancer to interact with the π promoter region in early stages of development.…”

Section: Resultsmentioning

confidence: 89%

“…A controversy has been raised arguing that there is no silencing in any part of the chicken α-globin locus. 21 This is based only in the study of active and repressive histone marks but no survey on the DNA methylation status of the regions was assessed. 21 Our results support combinatorial regulatory events which could be similar to those observed for RARβ2 gene expression, where the XPG endonuclease promotes DNA breaks and DNA demethylation at promoters, including CTCF recruitment and looping, which are events that can also be mediated by specific TAFs.…”

Section: -Hydroxymethylcytosine Dna Immunoprecipitation (Hmedip) Inmentioning

confidence: 99%

“…21 This is based only in the study of active and repressive histone marks but no survey on the DNA methylation status of the regions was assessed. 21 Our results support combinatorial regulatory events which could be similar to those observed for RARβ2 gene expression, where the XPG endonuclease promotes DNA breaks and DNA demethylation at promoters, including CTCF recruitment and looping, which are events that can also be mediated by specific TAFs. 41,42 This attempt to integrate genetic and epigenetic levels of regulation represents a starting point to address more detailed mechanistic questions.…”

Section: -Hydroxymethylcytosine Dna Immunoprecipitation (Hmedip) Inmentioning

confidence: 99%

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CTCF demarcates chicken embryonic α-globingene autonomous silencing and contributes to adult stage-specific gene expression

Valdes-Quezada¹,

Arriaga-Canon²,

Fonseca-Guzmán

et al. 2013

Epigenetics

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Genomic loci composed of more than one gene are frequently subjected to differential gene expression, with the chicken α-globin domain being a clear example. In the present study we aim to understand the globin switching mechanisms responsible for the epigenetic silencing of the embryonic π gene and the transcriptional activation of the adult α(D) and α(A) genes at the genomic domain level. In early stages, we describe a physical contact between the embryonic π gene and the distal 3' enhancer that is lost later during development. We show that such a level of regulation is achieved through the establishment of a DNA hypermethylation sub-domain that includes the embryonic gene and the adjacent genomic sequences. The multifunctional CCCTCC-binding factor (CTCF), which is located upstream of the α(D) gene promoter, delimits this sub-domain and creates a transition between the inactive sub-domain and the active sub-domain, which includes the adult α(D) gene. In avian-transformed erythroblast HD3 cells that are induced to differentiate, we found active DNA demethylation of the adult α(D) promoter, coincident with the incorporation of 5-hydroxymethylcytosine (5hmC) and concomitant with adult gene transcriptional activation. These results suggest that autonomous silencing of the embryonic π gene is needed to facilitate an optimal topological conformation of the domain. This model proposes that CTCF is contributing to a specific chromatin configuration that is necessary for differential α-globin gene expression during development.

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Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 89%

Section: -Hydroxymethylcytosine Dna Immunoprecipitation (Hmedip) Inmentioning

confidence: 99%

Section: -Hydroxymethylcytosine Dna Immunoprecipitation (Hmedip) Inmentioning

confidence: 99%

See 2 more Smart Citations

CTCF demarcates chicken embryonic α-globingene autonomous silencing and contributes to adult stage-specific gene expression

Valdes-Quezada¹,

Arriaga-Canon²,

Fonseca-Guzmán

et al. 2013

Epigenetics

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“…However, an activation effect of the LCR on Ε gene transcription seems very improbable. In this respect, it is of interest that in the chicken α-globin gene domain, the embryonic gene π also does not interact with any of the known distant regulatory elements of the domain [38]. It is thus likely that in the chicken, both α-type and β-type early embryonic globin genes possess an autonomous regulatory system.…”

Section: Discussionmentioning

confidence: 99%

Spatial organization of the chicken beta-globin gene domain in erythroid cells of embryonic and adult lineages

Ulianov

Гаврилов

Razin

2012

Epigenetics & Chromatin

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BackgroundThe β-globin gene domains of vertebrate animals constitute popular models for studying the regulation of eukaryotic gene transcription. It has previously been shown that in the mouse the developmental switching of globin gene expression correlates with the reconfiguration of an active chromatin hub (ACH), a complex of promoters of transcribed genes with distant regulatory elements. Although it is likely that observations made in the mouse β-globin gene domain are also relevant for this locus in other species, the validity of this supposition still lacks direct experimental evidence. Here, we have studied the spatial organization of the chicken β-globin gene domain. This domain is of particular interest because it represents the perfect example of the so-called ‘strong’ tissue-specific gene domain flanked by insulators, which delimit the area of preferential sensitivity to DNase I in erythroid cells.ResultsUsing chromosome conformation capture (3C), we have compared the spatial configuration of the β-globin gene domain in chicken red blood cells (RBCs) expressing embryonic (3-day-old RBCs) and adult (9-day-old RBCs) β-globin genes. In contrast to observations made in the mouse model, we found that in the chicken, the early embryonic β-globin gene, Ε, did not interact with the locus control region in RBCs of embryonic lineage (3-day RBCs), where this gene is actively transcribed. In contrast to the mouse model, a strong interaction of the promoter of another embryonic β-globin gene, ρ, with the promoter of the adult β-globin gene, βA, was observed in RBCs from both 3-day and 9-day chicken embryos. Finally, we have demonstrated that insulators flanking the chicken β-globin gene domain from the upstream and from the downstream interact with each other, which places the area characterized by lineage-specific sensitivity to DNase I in a separate chromatin loop.ConclusionsTaken together, our results strongly support the ACH model but show that within a domain of tissue-specific genes, the active status of a promoter does not necessarily correlate with the recruitment of this promoter to the ACH.

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Characterization of the enhancer element of the Danio rerio minor globin gene locus

Nefedochkina

Petrova

Ioudinkova

et al. 2016

Histochem Cell Biol

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In Danio rerio, the alpha- and beta-globin genes are present in two clusters: a major cluster located on chromosome 3 and a minor cluster located on chromosome 12. In contrast to the segregated alpha- and beta-globin gene domains of warm-blooded animals, in Danio rerio, each cluster contains both alpha- and beta-globin genes. Expression of globin genes present in the major cluster is controlled by an erythroid-specific enhancer similar to the major regulatory element of mammalian and avian alpha-globin gene domains. The enhancer controlling expression of the globin genes present in the minor locus has not been identified yet. Based on the distribution of epigenetic marks, we have selected two genomic regions that might harbor an enhancer of the minor locus. Using transient transfection of constructs with a reporter gene, we have demonstrated that a ~500-bp DNA fragment located ~1.7 Kb upstream of the αe4 gene possesses an erythroid-specific enhancer active with respect to promoters present in both the major and the minor globin gene loci of Danio rerio. The identified enhancer element harbors clustered binding sites for GATA-1, NF-E2, and EKLF similar to the enhancer of the major globin locus on chromosome 3. Both enhancers appear to have emerged as a result of independent evolution of a duplicated regulatory element present in an ancestral single alpha-/beta-globin locus that existed before teleost-specific genome duplication.

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The inactivation of the π gene in chicken erythroblasts of adult lineage is not mediated by packaging of the embryonic part of the α-globin gene domain into a repressive heterochromatin-like structure

Cited by 8 publications

References 52 publications

CTCF demarcates chicken embryonic α-globingene autonomous silencing and contributes to adult stage-specific gene expression

CTCF demarcates chicken embryonic α-globingene autonomous silencing and contributes to adult stage-specific gene expression

Spatial organization of the chicken beta-globin gene domain in erythroid cells of embryonic and adult lineages

Characterization of the enhancer element of the Danio rerio minor globin gene locus

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