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

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. We found that, similarly to mammalian genome, the chicken genome 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 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. Overall design: 5C and C-TALE analysis of chromatin spatial structure and total rRNA-depleted transcriptome sequencing in three chicken cultured cell lines

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Ulianov SV, Galitsyna AA, Flyamer IM, Golov AK, Khrameeva EE, Imakaev MV, Abdennur NA, Gelfand MS, Gavrilov AA, Razin SV