Hnrnpk is essential for embryonic limb bud development as a transcription activator and a collaborator of insulator protein Ctcf.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
12
03
2023
accepted:
04
08
2023
revised:
31
07
2023
pubmed:
23
8
2023
medline:
23
8
2023
entrez:
22
8
2023
Statut:
ppublish
Résumé
Proper development of the limb bud relies on the concordance of various signals, but its molecular mechanisms have not yet been fully illustrated. Here we report that heterogeneous nuclear ribonucleoprotein K (hnRNPK) is essential for limb bud development. Its ablation in the limb bud results in limbless forelimbs and severe deformities of the hindlimbs. In terms of mechanism, hnRNPK functions as a transcription activator for the vital genes involved in the three regulatory axes of limb bud development. Simultaneously, for the first time we elucidate that hnRNPK binds to and coordinates with the insulator protein CCCTC binding factor (CTCF) to maintain a three-dimensional chromatin architecture. Ablation of hnRNPK weakens the binding strength of CTCF to topologically associating domain (TAD) boundaries, then leading to the loose TADs, and decreased interactions between promoters and enhancers, and further decreased transcription of developmental genes. Our study establishes a fundamental and novel role of hnRNPK in regulating limb bud development.
Identifiants
pubmed: 37608075
doi: 10.1038/s41418-023-01207-z
pii: 10.1038/s41418-023-01207-z
pmc: PMC10589297
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2293-2308Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 92068105
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82172376
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82102518
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82072385
Organisme : China Postdoctoral Science Foundation
ID : 2021M693630
Informations de copyright
© 2023. The Author(s).
Références
Genes Dev. 2021 Nov 1;35(21-22):1490-1509
pubmed: 34711654
Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31231-31241
pubmed: 33229569
Nucleic Acids Res. 2020 Sep 18;48(16):9320-9335
pubmed: 32813011
Curr Opin Genet Dev. 2005 Jun;15(3):294-300
pubmed: 15917205
Mol Cell. 2019 Nov 7;76(3):412-422.e5
pubmed: 31522988
Genesis. 2002 Jun;33(2):77-80
pubmed: 12112875
Cell. 2017 May 18;169(5):930-944.e22
pubmed: 28525758
Nature. 2012 Apr 11;485(7398):376-80
pubmed: 22495300
J Bone Miner Res. 2015 Jun;30(6):1077-89
pubmed: 25556649
Nature. 1992 Mar 19;356(6366):215-21
pubmed: 1552940
Nat Protoc. 2018 May;13(5):1006-1019
pubmed: 29651053
Stem Cells. 2019 Feb;37(2):270-283
pubmed: 30372559
Science. 2009 Oct 9;326(5950):289-93
pubmed: 19815776
Nucleic Acids Res. 2001 Feb 1;29(3):638-43
pubmed: 11160884
Cell. 2011 Feb 4;144(3):327-39
pubmed: 21295696
Development. 2013 May;140(10):2130-8
pubmed: 23633510
Nat Commun. 2020 May 19;11(1):2491
pubmed: 32427842
Dev Biol. 2001 Aug 15;236(2):421-35
pubmed: 11476582
Nat Rev Genet. 2016 Oct 14;17(11):661-678
pubmed: 27739532
Methods Enzymol. 1993;225:361-73
pubmed: 8231863
Cell Syst. 2018 Feb 28;6(2):256-258.e1
pubmed: 29428417
Genesis. 2009 Apr;47(4):224-33
pubmed: 19298015
Chromosoma. 2014 Jun;123(3):217-24
pubmed: 24664318
Dev Cell. 2010 Dec 14;19(6):819-30
pubmed: 21145498
Curr Protoc Hum Genet. 2017 Jan 11;92:20.4.1-20.4.13
pubmed: 28075484
Curr Opin Genet Dev. 2007 Aug;17(4):359-66
pubmed: 17644373
Nat Methods. 2015 Dec;12(12):1143-9
pubmed: 26501517
Cell. 2011 Nov 23;147(5):1132-45
pubmed: 22118467
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W169-75
pubmed: 17576678
Int J Dev Biol. 2008;52(7):857-71
pubmed: 18956316
Development. 2005 Feb;132(4):797-803
pubmed: 15677727
Development. 2014 Oct;141(20):3934-43
pubmed: 25252942
Science. 2013 Jun 7;340(6137):1234167
pubmed: 23744951
Nat Rev Genet. 2017 Apr;18(4):245-258
pubmed: 28163321
Nat Genet. 1999 Jan;21(1):138-41
pubmed: 9916808
Methods Mol Biol. 2014;1130:113-121
pubmed: 24482169
Cancer Cell. 2015 Oct 12;28(4):486-499
pubmed: 26412324
Genome Res. 2018 Feb;28(2):192-202
pubmed: 29273625
Front Cell Dev Biol. 2017 Feb 28;5:14
pubmed: 28293554
Annu Rev Biochem. 1993;62:289-321
pubmed: 8352591
Dev Growth Differ. 2011 Feb;53(2):245-58
pubmed: 21338350
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Genome Biol. 2008;9(9):R137
pubmed: 18798982
RNA. 2002 Mar;8(3):265-78
pubmed: 12003487
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Bioinformatics. 2015 Jul 15;31(14):2382-3
pubmed: 25765347
Sci Rep. 2015 Dec 07;5:17732
pubmed: 26638989
Dev Biol. 2004 Dec 15;276(2):268-79
pubmed: 15581864
Nat Rev Genet. 2009 Dec;10(12):845-58
pubmed: 19920852
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Development. 2016 Aug 15;143(16):2994-3001
pubmed: 27402708
Nat Rev Genet. 2018 Dec;19(12):789-800
pubmed: 30367165
Genes Dev. 2014 Apr 1;28(7):723-34
pubmed: 24696455
Nat Commun. 2020 Aug 17;11(1):4133
pubmed: 32807777
Dev Biol. 2007 Jun 15;306(2):847-59
pubmed: 17448461
J Biol Chem. 2005 Apr 1;280(13):12690-9
pubmed: 15671036
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
EMBO J. 2013 Dec 11;32(24):3119-29
pubmed: 24185899
BMC Bioinformatics. 2020 Jul 20;21(1):319
pubmed: 32689928
Chromosome Res. 2020 Dec;28(3-4):381-393
pubmed: 33070289
Development. 1997 Jun;124(11):2235-44
pubmed: 9187149
Nat Commun. 2021 Sep 21;12(1):5557
pubmed: 34548488
Cell Res. 2014 May;24(5):513-31
pubmed: 24662484
Nat Genet. 2019 Aug;51(8):1263-1271
pubmed: 31358994
Cell Death Dis. 2022 Sep 20;13(9):803
pubmed: 36127325
Cell Rep. 2016 Dec 13;17(11):2913-2926
pubmed: 27974206
Genome Res. 2013 Dec;23(12):2066-77
pubmed: 24002784
Int J Dev Biol. 2002;46(7):963-7
pubmed: 12455635
Clin Sci (Lond). 2020 Jul 17;134(13):1763-1774
pubmed: 32619009
Cell. 2016 Oct 20;167(3):633-642.e11
pubmed: 27768887
Nature. 1996 Oct 3;383(6599):407-13
pubmed: 8837770
Genome Biol. 2015 Dec 01;16:259
pubmed: 26619908
Eur J Hum Genet. 2018 Sep;26(9):1272-1281
pubmed: 29904177
Nat Commun. 2019 Sep 13;10(1):4198
pubmed: 31519929
Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12390-12399
pubmed: 31147463
Nature. 2020 Jun;582(7812):432-437
pubmed: 32499643
Cell. 2005 Dec 16;123(6):1065-78
pubmed: 16360036
PLoS One. 2013 Nov 13;8(11):e79212
pubmed: 24236111
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):996-1001
pubmed: 24335803
Nature. 1995 Dec 14;378(6558):716-20
pubmed: 7501017
J Cell Biol. 2006 Mar 13;172(6):909-21
pubmed: 16533949
Dev Dyn. 2018 Dec;247(12):1253-1263
pubmed: 30325084
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8
pubmed: 19458158
Genet Med. 2020 Jan;22(1):189-198
pubmed: 31395945
PLoS Biol. 2018 Nov 26;16(11):e3000004
pubmed: 30475793
Genes Dev. 2018 Sep 1;32(17-18):1215-1225
pubmed: 30150253