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Epigenetic and genetic mechanisms in red cell biology. | LitMetric

Epigenetic and genetic mechanisms in red cell biology.

Curr Opin Hematol

aDepartment of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health bUW-Madison Blood Research Program, Carbone Cancer Center cDepartment of Biostatistics and Medical Informatics, Department of Statistics, Wisconsin Institutes for Medical Research, Madison, Wisconsin, USA.

Published: May 2014

AI Article Synopsis

  • Erythropoiesis is the process where hematopoietic stem cells turn into red blood cells, regulated by various chromatin modifying proteins, highlighting the role of genetic and epigenetic interactions in shaping the erythroid transcriptome.
  • Recent advancements show that small DNA motifs, known as cis-elements, are crucial for regulating gene expression by determining where transcription factors bind, although they often exist in abundance within the genome.
  • Understanding how cis-elements interact with chromatin can lead to new insights in disease mechanisms, and using genome-editing technologies could help pinpoint critical elements that affect red blood cell function and related disorders.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061918PMC
http://dx.doi.org/10.1097/MOH.0000000000000034DOI Listing

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