HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/L191    most recent 00385.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Yin, Z. Articles by Morrisey, E. E. Search for Related Content PubMed PubMed Citation Articles by Yin, Z. Articles by Morrisey, E. E.

Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression

Departments of ¹Medicine and ⁴Cell and Developmental Biology, University of Pennsylvania and ²Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and ³Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Submitted 8 September 2005 ; accepted in final form 21 February 2006

Hop is an unusual homeodomain protein that was first identified in the developing heart where it functions downstream of Nkx2.5 to modulate cardiac gene expression. Hop functions through interactions with histone deacetylase (HDAC) 2 to mediate repression of cardiac-specific genes, and recent studies show that HDAC activity and HDAC2 expression are decreased in people with chronic obstructive pulmonary disease. Here, we show that Hop is expressed in airway epithelium coincident with HDAC2, and expression is induced by the combination of dexamethasone and cAMP in parallel with induction of surfactant protein gene expression. Hop functions in the developing pulmonary airway, acting downstream of Nkx2.1 and GATA6, to negatively regulate surfactant protein expression. Loss of Hop expression in vivo results in defective type 2 pneumocyte development with increased surfactant production and disrupted alveolar formation. Thus Hop represents a novel regulator of pulmonary maturation that is induced by glucocorticoids to mediate functionally important HDAC-dependent negative feedback regulation.

homeodomain only protein; histone deacetylase

This article has been cited by other articles:

				K. Yamashita, M. S. Kim, H. L. Park, Y. Tokumaru, M. Osada, H. Inoue, M. Mori, and D. Sidransky HOP/OB1/NECC1 Promoter DNA Is Frequently Hypermethylated and Involved in Tumorigenic Ability in Esophageal Squamous Cell Carcinoma Mol. Cancer Res., January 1, 2008; 6(1): 31 - 41. [Abstract] [Full Text] [PDF]

				W. Shu, M. M. Lu, Y. Zhang, P. W. Tucker, D. Zhou, and E. E. Morrisey Foxp2 and Foxp1 cooperatively regulate lung and esophagus development Development, May 15, 2007; 134(10): 1991 - 2000. [Abstract] [Full Text] [PDF]

				K. G. Ackerman, J. Wang, L. Luo, Y. Fujiwara, S. H. Orkin, and D. R. Beier Gata4 Is Necessary for Normal Pulmonary Lobar Development Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 391 - 397. [Abstract] [Full Text] [PDF]

				Y. Maeda, V. Dave, and J. A. Whitsett Transcriptional Control of Lung Morphogenesis Physiol Rev, January 1, 2007; 87(1): 219 - 244. [Abstract] [Full Text] [PDF]