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p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network.

Abstract：

:We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues.

journal_name

Cell Rep

journal_title

Cell reports

authors

Marshall CB,Mays DJ,Beeler JS,Rosenbluth JM,Boyd KL,Santos Guasch GL,Shaver TM,Tang LJ,Liu Q,Shyr Y,Venters BJ,Magnuson MA,Pietenpol JA

doi

10.1016/j.celrep.2016.02.035

subject

Has Abstract

pub_date

2016-03-15 00:00:00

pages

2289-300

issue

10

issn

2211-1247

pii

S2211-1247(16)30138-3

journal_volume

14

pub_type

杂志文章

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