Identification of a novel epigenetic regulatory region within the pluripotency associated microRNA cluster, EEmiRC.
The miR-290 cluster is expressed in embryonic stem cells (ESCs) and is important for the maintenance of pluripotency, but little is known about the mechanisms regulating the early embryonic microRNA cluster (EEmiRC) expression. Here we report the identification of a 332-bp intragenic enhancer (IE) able to modulate the transcription of the mouse EEmiRC locus, presumably through binding of transcription modulators like Oct3/4, Sox2 and CTCF. This IE also contains a CpG island showing a differential pattern of DNA and histone methylation marks during differentiation of ESCs, which places EEmiRC in a novel regulatory feedback loop with DNA methylases. Deletion of IE significantly reduced the transcription of the EEmiRC, further proving the importance of this region in regulating the expression of EEmiRC.
Institute for Biochemistry and Molecular Biology, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Purushothama R
PR
Tata
Nageswara R
NR
Tata
Michael
M
Kühl
Ioan O
IO
Sirbu
D000818:Animals; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D050810:Octamer Transcription Factors / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D035683:MicroRNAs; D050810:Octamer Transcription Factors; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors
Stem Cells Dev. 2009 Sep;18(7):1093-108
19480567
Cell. 2009 Jun 26;137(7):1194-211
19563753
Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
19165215
Cell Res. 2008 Oct;18(10):985-96
18711447
Nat Genet. 1998 Jun;19(2):187-91
9620779
Nature. 2008 Oct 23;455(7216):1124-8
18806776
Nat Genet. 1999 Jan;21(1):103-7
9916800
Nat Biotechnol. 2009 May;27(5):459-61
19363475
Nature. 2009 Sep 24;461(7263):546-9
19734881
Cell. 2008 Aug 8;134(3):521-33
18692474
Nature. 2002 Sep 26;419(6905):407-11
12353038
Mamm Genome. 2009 Sep-Oct;20(9-10):573-80
19697081
RNA. 2010 May;16(5):1032-9
20348442
Genes Dev. 2009 Dec 15;23(24):2793-8
20008929
Genes Cells. 2007 Mar;12(3):387-96
17352742
Nat Genet. 2008 Dec;40(12):1478-83
18978791
Science. 2002 Nov 1;298(5595):1039-43
12351676
Wiley Interdiscip Rev Syst Biol Med. 2009 Sep-Oct;1(2):228-236
20016762
J Biol Chem. 2004 Apr 23;279(17):17063-9
14761969
Nat Struct Mol Biol. 2008 Mar;15(3):268-79
18311151
Mol Cell Biol. 2008 Oct;28(20):6473-82
18662993
Cell. 2006 Apr 21;125(2):315-26
16630819
Annu Rev Cell Dev Biol. 2001;17:435-62
11687496
Nucleic Acids Res. 1990 Mar 11;18(5):1145-52
2181400
RNA. 2005 Aug;11(8):1245-57
15987809
Nat Struct Mol Biol. 2008 Mar;15(3):259-67
18311153
Oncogene. 2002 Aug 12;21(35):5483-95
12154409
Cell Stem Cell. 2008 May 8;2(5):437-47
18462694
Nat Genet. 2006 Apr;38(4):431-40
16518401
J Biol Chem. 2008 Aug 8;283(32):21873-80
18539602
Nature. 2009 Jul 2;460(7251):128-32
19536159
Genome Res. 2009 Jan;19(1):24-32
19056695
Cell. 2008 Jun 13;133(6):1106-17
18555785
Genes Dev. 2007 Oct 15;21(20):2545-57
17938240
Dev Cell. 2003 Aug;5(2):351-8
12919684
Nat Protoc. 2007;2(5):1034-43
17546008
Nat Genet. 2000 Apr;24(4):372-6
10742100