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Series GSE70440 Query DataSets for GSE70440
Status Public on Aug 31, 2015
Title Loss of EZH2 results in precocious mammary gland development and the activation of STAT5-dependent genes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factor STAT5. As pregnancy progresses mammary signature genes are activated in a defined temporal order, which coincides with the recruitment of STAT5 to respective regulatory sequences. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy by STAT5, EZH1 and Pol II to these loci. Limited activation of differentiation-specific genes was also observed in mammary epithelium lacking both EZH2 and STAT5, suggesting a modulating but not mandatory role for STAT5. Notably, loss of EZH2 did not result in overt changes in genome-wide and gene-specific H3K27me3 patterns, suggesting that enhanced EZH1 recruitment can compensate for the loss of EZH2. Differentiated mammary epithelia failed to form in the combined absence of EZH1 and EZH2. Transplantation experiments failed to demonstrate a role for EZH2 in the biology of mammary stem and progenitor cells. In summary, while EZH1 and EZH2 serve redundant functions in the establishment of H3K27me3 and formation of mammary alveoli, the presence of EZH2 is required to obtain controlled temporal differentiation of mammary epithelium.
 
Overall design mRNA-seq in WT;MMTV-Cre (Control) at p13 and p18, E1-/- (E1KO), Ezh2f/f;MMTV-Cre(E2KO), Stat5f/f;MMTV-Cre(S5KO), and Ezh2f/f;Stat5f/f;MMTV-Cre (E2S5DKO) at p13 mammary tissues. ChIP-seq for H3K27me3, STAT5, EZH1, EZH2 and PolII in mammary tissues at p13
 
Contributor(s) Yoo KH, Oh S, Hensel T, Robinson GW, Kang K, Hennighausen L
Citation(s) 26250110, 27215382
Submission date Jul 01, 2015
Last update date May 15, 2019
Contact name Sumin Oh
E-mail(s) sumin.oh@nih.gov
Phone 301-496-8727
Organization name NIH
Department NIDDK
Lab LGP
Street address 9000 Rockville Pkie
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (41)
GSM1754886 ChIPSeq_E1KO_EZH1_rep1
GSM1754887 ChIPSeq_E2KO_EZH1_rep1
GSM1754888 ChIPSeq_E2KO_EZH1_rep2
Relations
BioProject PRJNA288691
SRA SRP060232

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Supplementary file Size Download File type/resource
GSE70440_RAW.tar 3.0 Gb (http)(custom) TAR (of BEDGRAPH, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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