KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]

Publication Date:
2018-02-16
Publisher:
Cold Spring Harbor Laboratory Press
Print ISSN:
0890-9369
Topics:
Biology
Published by:
http://www.cshlpress.com/
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autor Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
beschreibung Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D ( MLL4 ) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.
citation_standardnr 6166231
datenlieferant ipn_articles
feed_id 1644
feed_publisher Cold Spring Harbor Laboratory Press
feed_publisher_url http://www.cshlpress.com/
insertion_date 2018-02-16
journalissn 0890-9369
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Cold Spring Harbor Laboratory Press
quelle Genes & Development
relation http://genesdev.cshlp.org/cgi/content/short/32/2/181?rss=1
search_space articles
shingle_author_1 Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
shingle_author_2 Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
shingle_author_3 Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
shingle_author_4 Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
shingle_catch_all_1 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D ( MLL4 ) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.
Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_2 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D ( MLL4 ) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.
Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_3 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D ( MLL4 ) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.
Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_4 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D ( MLL4 ) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.
Lin-Shiao, E., Lan, Y., Coradin, M., Anderson, A., Donahue, G., Simpson, C. L., Sen, P., Saffie, R., Busino, L., Garcia, B. A., Berger, S. L., Capell, B. C.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_title_1 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
shingle_title_2 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
shingle_title_3 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
shingle_title_4 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
timestamp 2025-06-30T23:32:47.120Z
titel KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
titel_suche KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [Research Papers]
topic W
uid ipn_articles_6166231