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Series GSE73865 Query DataSets for GSE73865
Status Public on Jan 31, 2016
Title Genome-wide map of SIX2 and SIX1 binding in human embryonic kidney cortex
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Nephron endowment is determined by the self-renewal and induction of a nephron progenitor pool established at the onset of kidney development. In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors. Transient Six1 activity prefigures, and is essential for, active nephrogenesis. In contrast, Six2 maintains later progenitor self-renewal from the onset of nephrogenesis. We compared Six2’s regulatory actions in mouse and human nephron progenitors by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Surprisingly, SIX1 was identified as a SIX2 target unique to the human nephron progenitors. Further, RNA-seq and immunostaining revealed overlapping SIX1 and SIX2 progenitor activity in the 16 week human fetal kidney. Human SIX1 ChIP-seq revealed a similar set of targets to SIX2, and predicted both factors bind DNA through an identical recognition site. In contrast to the mouse where Six2 binds its own enhancers but doesn’t interact with DNA around Six1, both human SIX1 and SIX2 bind homologous SIX2 enhancers and putative enhancers positioned around SIX1. Transgenic analysis of a putative human SIX1 enhancer in the mouse revealed a transient, mouse-like, pre-nephrogenic, Six1 regulatory pattern. Together, these data demonstrate a divergence in SIX-factor regulation between mouse and human nephron progenitors. In the human, an auto/cross-regulatory loop drives continued SIX1 and SIX2 expression during active nephrogenesis. In contrast, the mouse establishes only an auto-regulatory Six2 loop. It is tempting to speculate that differential SIX-factor regulation may contribute to species differences in the duration of progenitor programs and nephron output.
Overall design Examination of SIX2, SIX1 binding profile in human embryonic kidney cortex and Six2 binding profile in mouse embryonic kidney using ChIP-Seq, with input DNA as negative control.
Contributor(s) O'Brien L, Guo Q, Valouev A, McMahon A
Citation(s) 26884396
Submission date Oct 08, 2015
Last update date May 15, 2019
Contact name Andrew P McMahon
Phone 323-442-7847
Organization name University of Southern California
Department Stem Cell Biol & Regen Med
Lab Andrew McMahon
Street address 1425 San Pablo St, BCC 312
City Los Angeles
State/province California
ZIP/Postal code 90033
Country USA
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (21)
GSM1904597 hSIX2_ChIPSeq_1
GSM1904598 hSIX2_ChIPSeq_2
GSM1904599 hSIX1_ChIPSeq_1
This SubSeries is part of SuperSeries:
GSE73867 Nephron endowment
BioProject PRJNA298244
SRA SRP064623

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Supplementary file Size Download File type/resource
GSE73865_RAW.tar 5.0 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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