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Article . 2016 . Peer-reviewed
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Article . 2017
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The regulatory repertoire of PLZF and SALL4 in undifferentiated spermatogonia

Authors: Dawn L. Lovelace; Zhen Gao; Kazadi Mutoji; Yuntao Charlie Song; Jianhua Ruan; Brian P. Hermann;

The regulatory repertoire of PLZF and SALL4 in undifferentiated spermatogonia

Abstract

Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout adulthood through balanced self-renewal and differentiation, yet the regulatory logic of these fate decisions is poorly understood. The transcription factors Sal-like 4 (SALL4) and zinc finger and BTB domain containing 16 (ZBTB16, aka: PLZF) are known to be required for normal SSC function, but their targets are largely unknown. ChIP-seq in THY1+ spermatogonia identified 4176 PLZF-bound and 2696 SALL4-bound genes, including 1149 and 515 which were unique to each factor, respectively, and 1295 which were bound by both factors. PLZF and SALL4 preferentially bound gene promoters and introns, respectively. Motif analyses identified putative PLZF and SALL4 binding sequences, but rarely both at shared sites indicating significant non-autonomous binding in any given cell. Indeed, the majority of PLZF/SALL4 shared sites contained only PLZF motifs. SALL4 also bound gene introns at sites containing motifs for the differentiation factor DMRT1. Moreover, mRNA levels for both unique and shared target genes involved in both SSC self-renewal and differentiation were suppressed following SALL4 or PLZF knockdown. Together, these data reveal the full profile of PLZF and SALL4 regulatory targets in undifferentiated spermatogonia, including SSCs, which will help elucidate mechanisms controlling the earliest cell fate decisions in spermatogenesis.

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Keywords

Male, Binding Sites, Genome, Gene Expression Profiling, Kruppel-Like Transcription Factors, Cell Differentiation, Molecular Sequence Annotation, Models, Biological, Spermatogonia, DNA-Binding Proteins, Gene Expression Regulation, Mice, Inbred DBA, Animals, Promyelocytic Leukemia Zinc Finger Protein, Glial Cell Line-Derived Neurotrophic Factor, Nucleotide Motifs, Spermatogenesis, Protein Binding, Signal Transduction, Transcription Factors

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    72
    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
72
Top 10%
Top 10%
Top 1%
bronze
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