CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus

被引：538

作者：

Splinter, Erik ^{[1
]}

Heath, Helen ^{[1
]}

Kooren, Jurgen ^{[1
]}

Palstra, Robert-Jan ^{[1
]}

Klous, Petra ^{[1
]}

Grosveld, Frank ^{[1
]}

Galjart, Niels ^{[1
]}

de Laat, Wouter ^{[1
]}

机构：

[1] Erasmus Med Ctr, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands

来源：

GENES & DEVELOPMENT | 2006年 / 20卷 / 17期

关键词：

CTCF; globin; insulator; higher-order chromatin structure; looping; transcription;

D O I：

10.1101/gad.399506

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

CTCF (CCCTC-binding factor) binds sites around the mouse beta-globin locus that spatially cluster in the erythroid cell nucleus. We show that both conditional deletion of CTCF and targeted disruption of a DNA-binding site destabilize these long-range interactions and cause local loss histone acetylation and gain of histone methylation, apparently without affecting transcription at the locus. Our data demonstrate that CTCF is directly involved in chromatin architecture and regulates local balance between active and repressive chromatin marks. We postulate that throughout the genome, relative position and stability of CTCF-mediated loops determine their effect on enhancer-promoter interactions, with gene insulation as one possible outcome.

引用

页码：2349 / 2354

页数：6

共 31 条

[1] The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].

Bell, AC ;

West, AG ;

Felsenfeld, G .

CELL, 1999, 98 (03) :387-396

[2] Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene [J].

Bell, AC ;

Felsenfeld, G .

NATURE, 2000, 405 (6785) :482-485

[3] Protein:protein interactions and the pairing of boundary elements in vivo [J].

Blanton, J ;

Gaszner, M ;

Schedl, P .

GENES & DEVELOPMENT, 2003, 17 (05) :664-675

[4] A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse β-globin locus [J].

Bulger, M ;

Schübeler, D ;

Bender, MA ;

Hamilton, J ;

Farrell, CM ;

Hardison, RC ;

Groudine, M .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (15) :5234-5244

[5] Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells [J].

Carotta, S ;

Pilat, S ;

Mairhofer, A ;

Schmidt, U ;

Dolznig, H ;

Steinlein, P ;

Beug, H .

BLOOD, 2004, 104 (06) :1873-1880

[6] Long-range chromatin regulatory interactions in vivo [J].

Carter, D ;

Chakalova, L ;

Osborne, CS ;

Dai, YF ;

Fraser, P .

NATURE GENETICS, 2002, 32 (04) :623-626

[7] CTCF, a candidate trans-acting factor for X-inactivation choice [J].

Chao, W ;

Huynh, KD ;

Spencer, RJ ;

Davidow, LS ;

Lee, JT .

SCIENCE, 2002, 295 (5553) :345-347

[8] Spatial organization of gene expression: the active chromatin hub [J].

de Laat, W ;

Grosveld, F .

CHROMOSOME RESEARCH, 2003, 11 (05) :447-459

[9] The vertebrate protein CTCF functions as an insulator in Saccharomyces cerevisiae [J].

Defossez, PA ;

Gilson, E .

NUCLEIC ACIDS RESEARCH, 2002, 30 (23) :5136-5141

[10] Capturing chromosome conformation [J].

Dekker, J ;

Rippe, K ;

Dekker, M ;

Kleckner, N .

SCIENCE, 2002, 295 (5558) :1306-1311

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