A facilitated tracking and transcription mechanism of long-range enhancer function
نویسندگان
چکیده
In the human epsilon-globin gene locus, the HS2 enhancer in the Locus Control Region regulates transcription of the embryonic epsilon-globin gene located over 10 kb away. The mechanism of long-range HS2 enhancer function was not fully established. Here we show that the HS2 enhancer complex containing the enhancer DNA together with RNA polymerase II (pol II) and TBP tracks along the intervening DNA, synthesizing short, polyadenylated, intergenic RNAs to ultimately loop with the epsilon-globin promoter. Guided by this facilitated tracking and transcription mechanism, the HS2 enhancer delivers pol II and TBP to the cis-linked globin promoter to activate mRNA synthesis from the target gene. An insulator inserted in the intervening DNA between the enhancer and the promoter traps the enhancer DNA and the associated pol II and TBP at the insulator site, blocking mid-stream the facilitated tracking and transcription mechanism of the enhancer complex, thereby blocking long-range enhancer function.
منابع مشابه
The LDB1 Complex Co-opts CTCF for Erythroid Lineage-Specific Long-Range Enhancer Interactions.
Lineage-specific transcription factors are critical for long-range enhancer interactions, but direct or indirect contributions of architectural proteins such as CCCTC-binding factor (CTCF) to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that an LDB1-bound enhancer upstream of carbonic anhyd...
متن کاملLong non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function
LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. However, LTR sequences are disproportionately present in human long, non-coding RNAs (lncRNAs). Whether and how the LTR lncRNAs serve biological functions are largely unknown. Here we show that in primary human erythroblasts, lncRNAs transcribed from the LTR retrotransposons of ERV-9 human endogenous retroviru...
متن کاملThe promoter targeting sequence facilitates and restricts a distant enhancer to a single promoter in the Drosophila embryo.
Transcriptional enhancers in large gene complexes activate promoters over huge distances, yet little is known about the mechanism of these long-range interactions. We report that the promoter targeting sequence (PTS) from the Abdominal-B locus of the Drosophila bithorax complex facilitates the activity of a distantly located enhancer in transgenic embryos and that it restricts the enhancer to a...
متن کاملAutonomous actions of the human growth hormone long-range enhancer
The human growth hormone (hGH) gene is controlled by a long-range enhancer, HSI, located 14.5 kb 5' to the hGH promoter. HSI establishes a domain of noncoding transcription that is 'looped' to the hGH promoter as an essential step in initiating hGH gene expression. Thus, defining how HSI generates its domain of noncoding transcription is central to understanding its long-range function. Here, w...
متن کاملSpatial enhancer clustering and regulation of enhancer-proximal genes by cohesin.
In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartm...
متن کامل