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Series GSE77586 Query DataSets for GSE77586
Status Public on Jun 06, 2016
Title The histone demethylase KDM6A controls the mammary luminal lineage through enzyme-independent mechanisms
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Mammary ducts and alveoli are composed of basal and luminal cells, with the fate and differentiation of secreting cells being controlled by hormones through specific transcription factors. This study establishes the essential role of the histone H3 lysine 27 trimethylation (H3K27me3) demethylase KDM6A (UTX) in a balanced basal and luminal cell compartment. Disproportionate formation of basal cells in the absence of KDM6A resulted in disorganized mammary ducts and alveoli and lactation failure. Mutant luminal progenitors lost their distinctive transcription factor expression pattern and acquired basal characteristics leading to a preferential expansion of this lineage. The structure of mammospheres obtained from mutant progenitors suggested they were derived from basal progenitors. The genomic H3K27me3 landscape was unaltered in the absence of KDM6A suggesting demethylase-independent mechanisms. In support of this, mammary tissue developed normally in mice expressing a catalytically inactive KDM6A. This study demonstrated that mammary luminal progenitor cells rely on UTX to stably maintain their identity and thereby establish a balance of basal and luminal cells required for a functional mammary gland.
Overall design mRNA-seq in WT;MMTV-Cre (Control) and Kdm6af/f;MMTV-Cre(Kdm6a KO) at virgin. ChIP-seq for KDM6A, and NFIB in mammary tissues at virgin and KDM6A KO H3K27me3, H3K4me1, PR, and ER in mammary tissues at p13.
Contributor(s) Yoo K, Oh S, Yang C, Kang K, Ge K, Robinson GW, Hennighausen L
Citation(s) 27215382
Submission date Feb 04, 2016
Last update date May 15, 2019
Contact name Sumin Oh
Phone 301-496-8727
Organization name NIH
Department NIDDK
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (13)
GSM2054799 ChIPSeq_WT_Vir_Input
GSM2054800 ChIPSeq_WT_Vir_UTX
GSM2054802 ChIPSeq_KO_Vir_UTX
BioProject PRJNA310874
SRA SRP069305

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Supplementary file Size Download File type/resource
GSE77586_RAW.tar 835.4 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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