title: Functional antagonism between Sall4 and Plzf defines germline progenitors.
abstract: Transcription factors required for formation of embryonic tissues often maintain their expression in adult stem cell populations, but whether their function remains equivalent is not clear. Here we demonstrate critical and distinct roles for Sall4 in development of embryonic germ cells and differentiation of postnatal spermatogonial progenitor cells (SPCs). In differentiating SPCs, Sall4 levels transiently increase and Sall4 physically interacts with Plzf, a transcription factor exclusively required for adult stem cell maintenance. Mechanistically, Sall4 sequesters Plzf to noncognate chromatin domains to induce expression of Kit, a target of Plzf-mediated repression required for differentiation. Plzf in turn antagonizes Sall4 function by displacing Sall4 from cognate chromatin to induce Sall1 expression. Taken together, these data suggest that transcription factors required for embryonic tissue development postnatally take on distinct roles through interaction with opposing factors, which hence define properties of the adult stem cell compartment.
authors.affiliation: Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Hobbs
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.forename: Antonella
authors.initials: A
authors.lastname: Papa
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Webster
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
authors.forename: Li
authors.initials: L
authors.lastname: Chai
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C509167:Sall4 protein, mouse; D014157:Transcription Factors; C092037:ZBTB16 protein, human