Multiple interactions between regulatory regions are required to stabilize an active chromatin hub

TY - JOUR

T1 - Multiple interactions between regulatory regions are required to stabilize an active chromatin hub

AU - Patrinos, George P

AU - de Krom, Mariken

AU - de Boer, Ernie

AU - Langeveld, An

AU - Imam, A M Ali

AU - Strouboulis, John

AU - de Laat, Wouter

AU - Grosveld, Frank G

PY - 2004/6/15

Y1 - 2004/6/15

N2 - The human beta-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration of the locus. It interacts with the genes and the hypersensitive regions flanking the locus to form an active chromatin hub (ACH) transcribing the genes. Proper developmental control of globin genes is largely determined by gene proximal regulatory sequences. Here, we provide the first functional evidence of the role of the most active sites of the LCR and the promoter of the beta-globin gene in the maintenance of the ACH. When the human beta-globin gene promoter is deleted in the context of a full LCR, the ACH is maintained with the beta-globin gene remaining in proximity. Additional deletion of hypersensitive site HS3 or HS2 of the LCR shows that HS3, but not HS2, in combination with the beta-globin promoter is crucial for the maintenance of the ACH at the definitive stage. We conclude that multiple interactions between the LCR and the beta-globin gene are required to maintain the appropriate spatial configuration in vivo.

AB - The human beta-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration of the locus. It interacts with the genes and the hypersensitive regions flanking the locus to form an active chromatin hub (ACH) transcribing the genes. Proper developmental control of globin genes is largely determined by gene proximal regulatory sequences. Here, we provide the first functional evidence of the role of the most active sites of the LCR and the promoter of the beta-globin gene in the maintenance of the ACH. When the human beta-globin gene promoter is deleted in the context of a full LCR, the ACH is maintained with the beta-globin gene remaining in proximity. Additional deletion of hypersensitive site HS3 or HS2 of the LCR shows that HS3, but not HS2, in combination with the beta-globin promoter is crucial for the maintenance of the ACH at the definitive stage. We conclude that multiple interactions between the LCR and the beta-globin gene are required to maintain the appropriate spatial configuration in vivo.

KW - Animals

KW - Chromatin/ultrastructure

KW - Globins/genetics

KW - Humans

KW - Locus Control Region/genetics

KW - Mice

KW - Mice, Transgenic

KW - Nucleic Acid Conformation

KW - Promoter Regions, Genetic

KW - Regulatory Sequences, Nucleic Acid/genetics

KW - Sequence Deletion

KW - Transcription, Genetic

U2 - 10.1101/gad.289704

DO - 10.1101/gad.289704

M3 - Article

C2 - 15198986

SN - 0890-9369

VL - 18

SP - 1495

EP - 1509

JO - Genes and Development

JF - Genes and Development

IS - 12

ER -