TY - JOUR
T1 - The Hippo Transducer TAZ Interacts with the SWI/SNF Complex to Regulate Breast Epithelial Lineage Commitment
AU - Skibinski, Adam
AU - Breindel, Jerrica L.
AU - Prat, Aleix
AU - Galván, Patricia
AU - Smith, Elizabeth
AU - Rolfs, Andreas
AU - Gupta, Piyush B.
AU - LaBaer, Joshua
AU - Kuperwasser, Charlotte
N1 - Funding Information:
We acknowledge Lisa Arendt and Sarah Phillips for their intellectual contributions and technical assistance. We would also like to thank Tim van Opijnen for advice and consultation regarding the screen, Karrie Southwell for assistance with the animal colony, and Stephen Lyle and Stephen Naber for reduction mammoplasty tissue procurement. This work was supported by grants from the Breast Cancer Research Foundation, the NIH/NICHD (R01HD073035), and the NIH/NCI (P01CA092644).
PY - 2014/3/27
Y1 - 2014/3/27
N2 - Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/. TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complexto modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.
AB - Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/. TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complexto modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.
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U2 - 10.1016/j.celrep.2014.02.038
DO - 10.1016/j.celrep.2014.02.038
M3 - Article
C2 - 24613358
AN - SCOPUS:84897104535
SN - 2211-1247
VL - 6
SP - 1059
EP - 1072
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -