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Cited by 19Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersChromosomal and Genetic Variations

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

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Ulianov, Sergey V., Galitsyna, Aleksandra A., Flyamer, Ilya M., Golov, Arkadiy K., Khrameeva, Ekaterina E., Imakaev, Maxim V., Abdennur, Nezar A., Gelfand, Mikhail S. +2 more·2017·Epigenetics & Chromatin
DOI 10.1186/s13072-017-0142-4PMC PMC5504709
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Abstract

BACKGROUND: In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation. RESULTS: We found that, similarly to mammalian genome, the chicken genomes is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream major regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation. CONCLUSIONS: Our findings demonstrate that the effects of tissue-specific transcription activation are not restricted to the host genomic locus but affect the overall chromatin structure and transcriptional output of the encompassing topologically associating domain.

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  • Changes in CTCF binding profiles seem to play an important role in the reconfiguration of the 3D genome during cell differentiation.

    “Changes in CTCF binding profiles seem to play an important role in the reconfiguration of the 3D genome during cell differentiation [95,96].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [95]

    The Discussion (page unavailable) reports that CTCF binding and the strength of CTCF-anchored loops decrease during HD3-cell differentiation, supporting a role in local chromatin contacts. It also says TAD and sub-TAD profiles show no dramatic or obvious changes despite the loss of binding, so this paper does not establish that changing CTCF binding profiles play an important role in broader 3D-genome reconfiguration. (LLM, conf=0.85)

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Authors
Ulianov, S. V., Galitsyna, A. A., Flyamer, I. M., Golov, A. K., Khrameeva, E. E., Imakaev, M. V., Abdennur, N. A., Gelfand, M. S., Gavrilov, A. A., & Razin, S. V.
Affiliations
  • Russian Academy of Sciences (RU)
  • Skolkovo Institute of Science and Technology (RU)
  • Massachusetts Institute of Technology (US)
  • National Research University Higher School of Economics (RU)
Corresponding author
Razin, Sergey V.
ORCID
Venue
Epigenetics & Chromatin
Publisher
Springer Science and Business Media LLC
Published
2017-07-11
Volume
10
Issue
1
Pages
35-35
ISSN
1756-8935 (ISSN-L)
DOI
10.1186/s13072-017-0142-4
PMC
PMC5504709
OpenAlex
W2735774597
Cited by
19
References
8
Citations by year
2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 5
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Epigenetics & Chromatin (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Russian Science Foundation (14-24-00022, 14-24-00155)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
alpha-globin gene cluster, terminal erythroid differentiation, topologically associating domains, chromatin compartments, CTCF binding, chromatin looping, intergenic transcription, housekeeping genes, gene deserts, lymphoid cells
MeSH terms
CCCTC-Binding Factor, Animals, Cell Line, Chickens, Chromatin, Erythropoiesis, Protein Binding, Transcriptional Activation, Up-Regulation, Genes, Essential, Avian Proteins, Erythroid Cells, alpha-Globins

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