BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

被引:105
作者
Kim, Shin-Il [1 ]
Bultman, Scott J. [2 ]
Kiefer, Christine M. [3 ]
Dean, Ann [3 ]
Bresnick, Emery H. [1 ]
机构
[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pharmacol, Madison, WI 53706 USA
[2] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
[3] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
chromatin; erythroid; GATA-1; globin; transcription; CHROMATIN DOMAIN ACTIVATION; HISTONE ACETYLATION PATTERN; TRANSCRIPTION FACTOR GATA-1; RNA-POLYMERASE-II; BINDING-PROTEIN; INTERGENIC TRANSCRIPTION; LYSINE; 9; GENE; COMPLEX; DNA;
D O I
10.1073/pnas.0806420106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The dynamic packaging of DNA into chromatin is a fundamental step in the control of diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote the formation of higher-order chromatin loops, the co-regulator machinery mediating loop assembly and disassembly is unknown. Using mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate that the Brg1 mutation abrogated a cell type-specific loop between the beta-globin locus control region and the downstream beta major promoter, despite trans-acting factor occupancy at both sites. By contrast, distinct loops were insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided additional evidence that BRG1 functions early in chromatin domain activation to mediate looping. Although the paradigm in which chromatin remodelers induce nucleosome structural transitions is well established, our results demonstrating an essential role of BRG1 in the genesis of specific chromatin loops expands the repertoire of their functions.
引用
收藏
页码:2259 / 2264
页数:6
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