PMID- 10431239
OWN - NLM
STAT- MEDLINE
DCOM- 19990826
LR  - 20071114
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 4
DP  - 1999 Aug
TI  - Klf4 is a transcription factor required for establishing the barrier function of 
      the skin.
PG  - 356-60
AB  - Located at the interface between body and environment, the epidermis must protect
      the body against toxic agents and dehydration, and protect itself against
      physical and mechanical stresses. Acquired just before birth and at the last
      stage of epidermal differentiation, the skin's proteinaceous/lipid barrier
      creates a surface seal essential for protecting animals against microbial
      infections and dehydration. We show here that Kruppel-like factor 4 (Klf4,
      encoded by the gene Klf4), highly expressed in the differentiating layers of
      epidermis, is both vital to and selective for barrier acquisition. Klf4-/- mice
      die shortly after birth due to loss of skin barrier function, as measured by
      penetration of external dyes and rapid loss of body fluids. The defect was not
      corrected by grafting of Klf4-/- skin onto nude mice. Loss of the barrier occurs 
      without morphological and biochemical alterations to the well-known structural
      features of epidermis that are essential for mechanical integrity. Instead,
      late-stage differentiation structures are selectively perturbed, including the
      cornified envelope, a likely scaffold for lipid organization. Using suppressive
      subtractive hybridization, we identified three transcripts encoding cornified
      envelope proteins with altered expression in the absence of Klf4. Sprr2a is one, 
      and is the only epidermal gene whose promoter is known to possess a functional
      Klf4 binding site. Our studies provide new insights into transcriptional
      governance of barrier function, and pave the way for unravelling the molecular
      events that orchestrate this essential process.
FAU - Segre, J A
AU  - Segre JA
AD  - Howard Hughes Medical Institute, Department of Molecular Genetics and Cell
      Biology, The University of Chicago, Illinois 60637, USA.
FAU - Bauer, C
AU  - Bauer C
FAU - Fuchs, E
AU  - Fuchs E
LA  - eng
GR  - AR31737/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GKLF protein)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - *DNA-Binding Proteins
MH  - Epidermis/anatomy & histology/embryology/*physiology/ultrastructure
MH  - Kruppel-Like Transcription Factors
MH  - Mice
MH  - Mice, Nude
MH  - Microscopy, Immunoelectron
MH  - Models, Genetic
MH  - Mutagenesis
MH  - Skin Transplantation
MH  - Time Factors
MH  - Tongue/anatomy & histology/embryology
MH  - Transcription Factors/analysis/metabolism/*physiology
EDAT- 1999/08/04 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/08/04 10:00
PHST- 1999/08/04 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/08/04 10:00 [entrez]
AID - 10.1038/11926 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Aug;22(4):356-60. doi: 10.1038/11926.