2026-05-22T23:34:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/188962024-11-29T20:04:40Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Beucher, Anthony
author
Miguel-Escalada, Irene
author
Balboa, Diego
author
De Vas, Matías G
author
Maestro, Miguel Angel
author
Garcia-Hurtado, Javier
author
Bernal, Aina
author
Gonzalez-Franco, Roser
author
Vargiu, Pierfrancesco
author
Heyn, Holger
author
Ravassard, Philippe
author
Ortega, Sagrario
author
Ferrer, Jorge
funder
UK Research and Innovation
funder
Wellcome Trust
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Ciencia y Universidades (España)
funder
NIHR - Imperial Biomedical Research Centre (Reino Unido)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Centres de Recerca de Catalunya (CERCA)
2024-03-07T08:42:56Z
2024-03-07T08:42:56Z
2022-10
Nat Cell Biol . 2022 ;24(10):1528-1540.
10.1038/s41556-022-00996-8
1476-4679
Nature cell biology
36202974
http://hdl.handle.net/20.500.12105/18896
The biological purpose of long non-coding RNAs (lncRNAs) is poorly understood. Haploinsufficient mutations in HNF1A homeobox A (HNF1A), encoding a homeodomain transcription factor, cause diabetes mellitus. Here, we examine HASTER, the promoter of an lncRNA antisense to HNF1A. Using mouse and human models, we show that HASTER maintains cell-specific physiological HNF1A concentrations through positive and negative feedback loops. Pancreatic β cells from Haster mutant mice consequently showed variegated HNF1A silencing or overexpression, resulting in hyperglycaemia. HASTER-dependent negative feedback was essential to prevent HNF1A binding to inappropriate genomic regions. We demonstrate that the HASTER promoter DNA, rather than the lncRNA, modulates HNF1A promoter-enhancer interactions in cis and thereby regulates HNF1A transcription. Our studies expose a cis-regulatory element that is unlike classic enhancers or silencers, it stabilizes the transcription of its target gene and ensures the fidelity of a cell-specific transcription factor program. They also show that disruption of a mammalian lncRNA promoter can cause diabetes mellitus.
eng
The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A.
journal article
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
URL
https://repisalud.isciii.es/bitstreams/5968543d-165c-47ba-b070-d31620bceaa0/download
File
MD5
e53c4b0aba6c771a3fd52ffe7ed49b8b
15609901
application/pdf
TheHASTERlncRNApromoter_2022.pdf
URL
https://repisalud.isciii.es/bitstreams/0a7bb711-f63c-4781-a3aa-80cd0940394a/download
File
MD5
cd2c8624bc9bb96aa0356a375f17cc52
3665987
application/pdf
41556_2022_996_MOESM1_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/9311598e-386c-4452-8067-137c0b2a1a4b/download
File
MD5
d69430e88839059c9eea5453898aa084
2032949
application/pdf
41556_2022_996_MOESM2_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/77e99351-17b8-4ff4-b022-39840e0e308c/download
File
MD5
e1f6dad2d10221d8bd5e1a054cae5121
11907330
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM3_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/36c4be8a-ac66-43a9-b34f-7470bb37866e/download
File
MD5
606f6de225748d748b58fa4f65527d71
17554
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM4_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/ac73abd8-1629-4dd5-b7f0-157dd4bca9e6/download
File
MD5
410f579d1266b86ee059ff01877e3529
7037884
application/pdf
41556_2022_996_MOESM5_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/e12b52d2-7f6b-4906-af53-6f721a62fc7c/download
File
MD5
405eeb93756010eab99a16f47285f2f9
10441
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM6_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/19d33aa0-1be7-4ca9-b299-d1aa85a17411/download
File
MD5
d4e039f2edb8ca79e6b0a99f4f577f71
18443
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM7_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/9195fd37-42bd-4f3a-b4cf-43a373a5fcb2/download
File
MD5
3281b4f291bc4ba4136094e738feb15b
20914
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM8_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/0bf26551-d2ef-47c5-8404-1e31208fcca1/download
File
MD5
01677ce04a4a7af53a8cc637ab1872f5
13232
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM9_ESM(1).xlsx
URL
https://repisalud.isciii.es/bitstreams/16d71623-bf0b-48fb-a8c4-c6826f7f9b8d/download
File
MD5
257cd893c535e249f9cd1c485428dacb
14362
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM10_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/4f5b012f-c55f-4cf7-a4cc-ae68c41bea6c/download
File
MD5
031755cab6cbf3dba1593677d1d5e65f
10713
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM11_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/c9c4b1d2-2a61-471c-afca-3f289ae0ea2d/download
File
MD5
95e1b16b574bbfc77e18dbff625f7d85
9417
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM12_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/75aba1d0-8379-466f-98a3-0e4d973760bb/download
File
MD5
3ee14eac40f4e32869dc4c218afce5cd
9974
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM13_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/b0a51431-807d-4d12-aadb-71dfe15bf613/download
File
MD5
adf168e60a6c92e370faa9d68211e5a1
11406
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM14_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/22e61a06-ee16-4806-b61b-b6b1c4ecfe0c/download
File
MD5
42c42d3b1e9603317097c7ea38330fe0
1958040
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM15_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/73a382ec-3bb2-4784-8b62-d58db2b0216e/download
File
MD5
0cb2e194aeff34bea1d45fc5e52eb53a
17628
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM16_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/e926968d-e852-468c-8296-e9a17b445abe/download
File
MD5
c9c38c24987645923b21d19d984b3d2c
9632
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM17_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/0bf38a6f-1868-4d8f-b723-2f00bb07d3f9/download
File
MD5
eae0179fbdf0307e50a2ed810427adad
10040
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM18_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/93388bad-dbab-4ec0-80fd-71b7c0a13356/download
File
MD5
0c8eec29083442edaa3f0656da6d337d
13762
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM19_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/867c64e9-7da2-47bc-98e8-d822f69c0085/download
File
MD5
91474a416ac368cec908e64c84c6571c
14002
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
41556_2022_996_MOESM20_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/30255bbe-c3b5-43e4-a842-3909aeb5e29a/download
File
MD5
504de2d7fa6a1adf5e62fa3763daa854
134526
text/plain
TheHASTERlncRNApromoter_2022.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/341f08fc-550b-457d-8681-ccab28d7f6c6/download
File
MD5
28f4ef3f469eed610e8109fe3bdf5707
17
text/plain
41556_2022_996_MOESM1_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/2770a271-8304-4bed-9006-9dce71edee69/download
File
MD5
0fe88915c155f1a57dc7df931266cd67
146331
text/plain
41556_2022_996_MOESM2_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/02036752-6115-4eed-aab8-33ed21d3ef66/download
File
MD5
410979cff778c77ae339b3b74eea485a
364
text/plain
41556_2022_996_MOESM5_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/bc2b81f2-61db-4807-84fb-969153935941/download
File
MD5
26d3ad0c41afeb1b747ed41610a21b11
100000
text/plain
41556_2022_996_MOESM3_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/bf86cdae-2f50-4d92-8e6b-64479d45d4a0/download
File
MD5
ee0da1bc62caeb76696cb97386fa19bd
5224
text/plain
41556_2022_996_MOESM4_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/a2978a9d-ca49-4f08-b2e4-8cf330ab4f9c/download
File
MD5
87b0a868131aaa2f388b8ba95fa6b5ca
1769
text/plain
41556_2022_996_MOESM6_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/5b2695f7-0515-4f1a-9b07-0262641320ae/download
File
MD5
01154ff034f25a91990806581a59aff0
5499
text/plain
41556_2022_996_MOESM7_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/6639f774-b86f-4fd2-8508-0b6c52c2636c/download
File
MD5
e9c480223825c1c9fe02ea0553063f3c
6635
text/plain
41556_2022_996_MOESM8_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/b092f3c0-ab4e-4310-bef9-3776af42caa8/download
File
MD5
99ffd9476dda920cd2a275ce44df138c
4420
text/plain
41556_2022_996_MOESM9_ESM(1).xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/dfc3c7fe-a64d-45a7-b2b6-416bcebaeab4/download
File
MD5
a3fad379410052723c1e402c3870b980
5429
text/plain
41556_2022_996_MOESM10_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/ec91d238-3925-4755-8c92-d2d7c933d202/download
File
MD5
bfabc288909065d4d60e71dedbda38ab
1721
text/plain
41556_2022_996_MOESM11_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/32912ec1-82ad-417f-8c6e-b58a90adea90/download
File
MD5
da48c9fc156e5d779ca6d59803cea7d7
457
text/plain
41556_2022_996_MOESM12_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/25869d9e-e87f-48bb-b81c-12bc09024bde/download
File
MD5
6a1fd0cc339628693b63f0d3f61210b6
1212
text/plain
41556_2022_996_MOESM13_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/ecfe32e0-9ab2-41cb-b2b9-6b4a0311f642/download
File
MD5
4f47e80072371f2c1a92c44ef9b8d635
1678
text/plain
41556_2022_996_MOESM14_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/4225e061-451e-4e27-bd17-255e404113e6/download
File
MD5
feb24c68952113f4b7d5902a9d70e87b
100000
text/plain
41556_2022_996_MOESM15_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/5149ece3-46ac-4e7b-9822-d5bfda768c6e/download
File
MD5
dc07fd98feb74432ec323b9095e6b55b
6172
text/plain
41556_2022_996_MOESM16_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/5da5ae12-f775-4a82-a0a6-396ab4755911/download
File
MD5
5ff12214d5bfd98deb3666c7dfa7afa2
647
text/plain
41556_2022_996_MOESM17_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/1aa64f9e-3129-4696-81bc-7bba3bed88e3/download
File
MD5
e059300d941a481f465f193e613fa27c
1793
text/plain
41556_2022_996_MOESM18_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/65055561-f145-4e63-8426-a7d65ef25da5/download
File
MD5
e0bfc283a5c81a16dacfc12e1afadcaa
2740
text/plain
41556_2022_996_MOESM19_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/57c95139-a11b-4364-b13e-9506d4249aef/download
File
MD5
910d02cec090b34c35abad7df50e43f6
6828
text/plain
41556_2022_996_MOESM20_ESM.xlsx.txt