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

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.

Авторы: Ulianov Sergey V., Galitsyna Aleksandra A., Flyamer Ilya M., Golov Arkadiy K., Khrameeva Ekaterina E., Imakaev Maxim V., Abdennur Nezar A., Gelfand Mikhail S., Gavrilov Alexey A., Razin Sergey V.
Журнал: Epigenetics and Chromatin
Том: 10
Номер: 1
Год издания: 2017
Издательство: BioMed Central
Местоположение издательства: London
Первая страница: 35
DOI: 10.1186/s13072-017-0142-4
Аннотация: Background: In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid diferentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the infuence of the erythroid-specifc 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 profle, 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 diferentiation. 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 diferentiated 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 signifcantly decompacted in diferentiated 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 diferentiation. Conclusions: Our fndings demonstrate that the efects of tissue-specifc transcription activation are not restricted to the host genomic locus but afect the overall chromatin structure and transcriptional output of the encompassing topologically associating domain.
Добавил в систему: Ульянов Сергей Владимирович

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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 structureстатья

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