Differential roles of Sall4 isoforms in embryonic stem cell pluripotency. Mol Cell Biol 2010 Nov;30(22):5364-80
Date
09/15/2010Pubmed ID
20837710Pubmed Central ID
PMC2976381DOI
10.1128/MCB.00419-10Scopus ID
2-s2.0-78649551191 (requires institutional sign-in at Scopus site) 148 CitationsAbstract
Murine embryonic stem (ES) cells are defined by continuous self-renewal and pluripotency. A diverse repertoire of protein isoforms arising from alternative splicing is expressed in ES cells without defined biological roles. Sall4, a transcription factor essential for pluripotency, exists as two isoforms (Sall4a and Sall4b). Both isoforms can form homodimers and a heterodimer with each other, and each can interact with Nanog. By genomewide location analysis, we determined that Sall4a and Sall4b have overlapping, but not identical binding sites within the ES cell genome. In addition, Sall4b, but not Sall4a, binds preferentially to highly expressed loci in ES cells. Sall4a and Sall4b binding sites are distinguished by both epigenetic marks at target loci and their clustering with binding sites of other pluripotency factors. When ES cells expressing a single isoform of Sall4 are generated, Sall4b alone could maintain the pluripotent state, although it could not completely suppress all differentiation markers. Sall4a and Sall4b collaborate in maintenance of the pluripotent state but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells.
Author List
Rao S, Zhen S, Roumiantsev S, McDonald LT, Yuan GC, Orkin SHAuthor
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Cell Differentiation
Cells, Cultured
DNA-Binding Proteins
Dimerization
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Homeodomain Proteins
Humans
Mice
Microarray Analysis
Molecular Sequence Data
Nanog Homeobox Protein
Pluripotent Stem Cells
Protein Isoforms
Protein Structure, Quaternary
Transcription Factors
