Epigenetic and Genetic Mechanisms in Red Cell Biology

Overview

Journal Curr Opin Hematol

Specialty Hematology

Date 2014 Apr 12

PMID 24722192

Citations 6

Authors

Kyle J Hewitt

Rajendran Sanalkumar

Kirby D Johnson

Sunduz Keles

Emery H Bresnick

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Erythropoiesis, in which hematopoietic stem cells (HSCs) generate lineage-committed progenitors that mature into erythrocytes, is regulated by numerous chromatin modifying and remodeling proteins. We will focus on how epigenetic and genetic mechanisms mesh to establish the erythroid transcriptome and how studying erythropoiesis can yield genomic principles.

Recent Findings: Trans-acting factor binding to small DNA motifs (cis-elements) underlies regulatory complex assembly at specific chromatin sites, and therefore unique transcriptomes. As cis-elements are often very small, thousands or millions of copies of a given element reside in a genome. Chromatin restricts factor access in a context-dependent manner, and cis-element-binding factors recruit chromatin regulators that mediate functional outputs. Technologies to map chromatin attributes of loci in vivo, to edit genomes and to sequence whole genomes have been transformative in discovering critical cis-elements linked to human disease.

Summary: Cis-elements mediate chromatin-targeting specificity, and chromatin regulators dictate cis-element accessibility/function, illustrating an amalgamation of genetic and epigenetic mechanisms. Cis-elements often function ectopically when studied outside of their endogenous loci, and complex strategies to identify nonredundant cis-elements require further development. Facile genome-editing technologies provide a new approach to address this problem. Extending genetic analyses beyond exons and promoters will yield a rich pipeline of cis-element alterations with importance for red cell biology and disease.

Citing Articles

Association of DDX5/p68 protein with the upstream erythroid enhancer element (EHS1) of the gene encoding the KLF1 transcription factor.

Chen X, Pillay S, Lohmann F, Bieker J J Biol Chem. 2023; 299(12):105489.

PMID: 38000658 PMC: 10750184. DOI: 10.1016/j.jbc.2023.105489.

Stage-specific dual function: EZH2 regulates human erythropoiesis by eliciting histone and non-histone methylation.

Li M, Liu D, Xue F, Zhang H, Yang Q, Sun L Haematologica. 2023; 108(9):2487-2502.

PMID: 37021526 PMC: 10483364. DOI: 10.3324/haematol.2022.282016.

When Pol II sees red.

Xie M, Bungert J Blood. 2021; 138(18):1648-1649.

PMID: 34735000 PMC: 8569415. DOI: 10.1182/blood.2021012453.

The chromatin-remodeling enzyme Smarca5 regulates erythrocyte aggregation via Keap1-Nrf2 signaling.

Ding Y, Li Y, Zhao Z, Zhang Q, Liu F Elife. 2021; 10.

PMID: 34698638 PMC: 8594921. DOI: 10.7554/eLife.72557.

The histone methyltransferase inhibitor A-366 enhances hemoglobin expression in erythroleukemia cells upon co-exposure with chemical inducers in culture.

Papagiannopoulos C, Theodoroula N, Kyritsis K, Akrivou M, Kosmidou M, Tsouderou K J Biol Res (Thessalon). 2021; 28(1):2.

PMID: 33407944 PMC: 7788816. DOI: 10.1186/s40709-020-00132-3.

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