| First Author | Kim SI | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 12 | Pages | 4551-65 |
| PubMed ID | 17438135 | Mgi Jnum | J:122357 |
| Mgi Id | MGI:3714110 | Doi | 10.1128/MCB.00235-07 |
| Citation | Kim SI, et al. (2007) Dissecting molecular steps in chromatin domain activation during hematopoietic differentiation. Mol Cell Biol 27(12):4551-65 |
| abstractText | GATA factors orchestrate hematopoiesis via multistep transcriptional mechanisms, but the interrelationships and importance of individual steps are poorly understood. Using complementation analysis with GATA-1-null cells and mice containing a hypomorphic allele of the chromatin remodeler BRG1, we dissected the pathway from GATA-1 binding to cofactor recruitment, chromatin loop formation, and transcriptional activation. Analysis of GATA-1-mediated activation of the beta-globin locus, in which GATA-1 assembles dispersed complexes at the promoters and the distal locus control region (LCR), revealed molecular intermediates, including GATA-1-independent and GATA-1-containing LCR subcomplexes, both defective in promoting loop formation. An additional intermediate consisted of an apparently normal LCR complex and a promoter complex with reduced levels of total RNA polymerase II (Pol II) and Pol II phosphorylated at serine 5 of the carboxy-terminal domain. Reduced BRG1 activity solely compromised Pol II and serine 5-phosphorylated Pol II occupancy at the promoter, phenocopying the LCR-deleted mouse. These studies defined a hierarchical order of GATA-1-triggered events at a complex locus and establish a novel mechanism of long-range gene regulation. |
