Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the beta-globin locus control region.
Locus control regions (LCRs) are regulatory DNA sequences that are situated many kilobases away from their cognate promoters. LCRs protect transgenes from position effect variegation and heterochromatinization and also promote copy-number dependence of the levels of transgene expression. In this work, we describe the biochemical purification of a previously undescribed LCR-associated remodeling complex (LARC) that consists of heterogeneous nuclear ribonucleoprotein C1/C2, nucleosome remodeling SWI/SNF, and nucleosome remodeling and deacetylating (NuRD)/MeCP1 as a single homogeneous complex. LARC binds to the hypersensitive 2 (HS2)-Maf recognition element (MARE) DNA in a sequence-specific manner and remodels nucleosomes. Heterogeneous nuclear ribonucleoprotein C1/C2, previously known as a general RNA binding protein, provides a sequence-specific DNA recognition element for LARC, and the LARC DNA-recognition sequence is essential for the enhancement of transcription by HS2. Independently of the initiation of transcription, LARC becomes associated with beta-like globin promoters.
Mahajan
Milind C
MC
Department of Genetics, The Anlyan Center, Yale University School of Medicine, New Haven, CT 06511, USA.
Narlikar
Geeta J
GJ
Boyapaty
Gokul
G
Kingston
Robert E
RE
Weissman
Sherman M
SM
D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D019901:Locus Control Region; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C503635:HNRNPC protein, human; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; C489689:MeCP1 histone deacetylase complex, human; D046912:Multiprotein Complexes; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D005914:Globins; D006655:Histone Deacetylases