An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression
(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.
(Less)
- author
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 7448
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85143126603
- pmid:36460642
- 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
- 2024-06-26 01:33:14
@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}}, }