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An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression

Dinh, Thanh Theresa ; Xiang, Menglan ; Rajaraman, Anusha ; Wang, Yongzhi LU ; Salazar, Nicole ; Zhu, Yu ; Roper, Walter ; Rhee, Siyeon ; Brulois, Kevin and O’Hara, Ed , et al. (2022) In Nature Communications 13(1).
Abstract

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors.... (More)

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
13
issue
1
article number
7448
publisher
Nature Publishing Group
external identifiers
  • pmid:36460642
  • scopus:85143126603
ISSN
2041-1723
DOI
10.1038/s41467-022-34991-2
language
English
LU publication?
yes
id
70f108ad-1883-484a-bdf6-cbd20988f89d
date added to LUP
2022-12-23 10:46:13
date last changed
2024-04-30 19:51:20
@article{70f108ad-1883-484a-bdf6-cbd20988f89d,
  abstract     = {{<p>Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3<sup>+</sup> capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.</p>}},
  author       = {{Dinh, Thanh Theresa and Xiang, Menglan and Rajaraman, Anusha and Wang, Yongzhi and Salazar, Nicole and Zhu, Yu and Roper, Walter and Rhee, Siyeon and Brulois, Kevin and O’Hara, Ed and Kiefel, Helena and Dinh, Truc M. and Bi, Yuhan and Gonzalez, Dalila and Bao, Evan P. and Red-Horse, Kristy and Balogh, Peter and Gábris, Fanni and Gaszner, Balázs and Berta, Gergely and Pan, Junliang and Butcher, Eugene C.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-34991-2}},
  doi          = {{10.1038/s41467-022-34991-2}},
  volume       = {{13}},
  year         = {{2022}},
}