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 structureReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

Epigenetics and Chromatin

, 10:35

First Online: 11 July 2017Received: 29 December 2016Accepted: 03 July 2017

Abstract

BackgroundIn 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.

ResultsWe 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.

ConclusionsOur 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.

KeywordsAlpha-globin genes Transcription CTCF Chromatin spatial structure TAD Chromatin compartment Abbreviations3Cchromosome conformation capture

3Dthree-dimensional

5Cchromatin conformation capture carbon copy

ACHactive chromatin hub

AgGDalpha-globin gene domain

bpbase pair

CBSCTCF-binding site

ChIP-seqchromatin immunoprecipitation followed with deep sequencing

C-TALEChromosome TArget Ligation Enrichment

ESCembryonic stem cells

IMPintegrative modeling platform

Kbpkilobases, thousands of base pairs

Mbmegabases, millions of base pairs

MREmajor regulatory element

PCAprincipal component analysis

TADtopologically associating domain

Electronic supplementary materialThe online version of this article doi:10.1186-s13072-017-0142-4 contains supplementary material, which is available to authorized users.

Sergey V. Ulianov and Aleksandra A. Galitsyna have contributed equally to this work

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Author: Sergey V. Ulianov - Aleksandra A. Galitsyna - Ilya M. Flyamer - Arkadiy K. Golov - Ekaterina E. Khrameeva - Maxim V. I

Source: https://link.springer.com/



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