13 November 2025, 10:00
Connecting transcriptional enhancers with promoters in health and disease
Description AbstractThe mechanisms underlying specific enhancer promoter E P pairing remain largely unclear While chromosome extrusion by cohesin has been proposed to facilitate E P proximity cohesin loss affects only a small subset of genes suggesting additional factors mediate spatial regulatory connections Beyond the generic CTCF cohesin machinery few nuclear factors have been examined through acute perturbation to determine their direct role in physically linking regulatory elements Through acute degradation experiments we discovered that the transcription co factor LDB1 spatially connects a substantial fraction of E P loops LDB1 exerts this function in cooperation with single stranded DNA binding proteins SSBPs Leveraging the dynamic re establishment of nuclear architecture during the transition from mitosis to G1 phase we established a relationship between LDB1 dependent chromatin occupancy and loop formation Region Capture Micro C RCMC and Tri C experiments revealed that LDB1 organizes multi enhancer networks to activate transcription Using multiple degron systems I will outlined the varied yet limited influence of CTCF cohesin and the chromosome loop extrusion factor NIPBL on LDB1 dependent regulatory connectivity The adapter molecule LMO2 which links LDB1 to transcription factors at specific genomic loci is frequently overexpressed in T Cell Acute Lymphoblastic Leukemia T ALL I will present recent studies LDB1 s role in spatially connecting enhancers to oncogenes in T ALL In sum I look forward to discussing how the LDB1 complex spatially organizes the mammalian genome in normal and cancerous cells About the speaker Biographical information about the speaker Meet the speakerTo meet with the speaker informally after the talks sign up here add link We especially encourage predocs and postdocs to take advantage of this opportunity Attachments Link to a file for example a pdf of the seminar s programme the file can be uploaded on the intranet Connection detailsZoom link Meeting ID XXXXXXXXX Password XXXXXXX Please note that the talk will yes not be recorded For the FAQ section as a zoom participant please use either the chat function the host will read out your question or the raise your hand function and turn on your microphone... AbstractThe mechanisms underlying specific enhancer-promoter (E-P) pairing remain largely unclear. While chromosome extrusion by cohesin has been proposed to facilitate E-P proximity, cohesin loss affects only a small subset of genes, suggesting additional factors mediate spatial regulatory connections. Beyond the generic CTCF/cohesin machinery, few nuclear factors have been examined through acute perturbation to determine their direct role in physically linking regulatory elements. Through acute degradation experiments, we discovered that the transcription co-factor LDB1 spatially connects a substantial fraction of E-P loops. LDB1 exerts this function in cooperation with single-stranded DNA binding proteins (SSBPs). Leveraging the dynamic re-establishment of nuclear architecture during the transition from mitosis to G1-phase, we established a relationship between LDB1-dependent...
Speaker(s): Gerd Blobel, Professor of Pediatrics (Hematology)
Perelman School of Medicine
University of Pennsylvania, USA
Host: Eileen Furlong
Place: Small Operon
EMBL Heidelberg
Additional information
Abstract
The mechanisms underlying specific enhancer-promoter (E-P) pairing remain largely unclear. While chromosome extrusion by cohesin has been proposed to facilitate E-P proximity, cohesin loss affects only a small subset of genes, suggesting additional factors mediate spatial regulatory connections. Beyond the generic CTCF/cohesin machinery, few nuclear factors have been examined through acute perturbation to determine their direct role in physically linking regulatory elements. Through acute degradation experiments, we discovered that the transcription co-factor LDB1 spatially connects a substantial fraction of E-P loops. LDB1 exerts this function in cooperation with single-stranded DNA binding proteins (SSBPs). Leveraging the dynamic re-establishment of nuclear architecture during the transition from mitosis to G1-phase, we established a relationship between LDB1-dependent chromatin occupancy and loop formation. Region-Capture-Micro-C (RCMC) and Tri-C experiments revealed that LDB1 organizes multi-enhancer networks to activate transcription. Using multiple degron systems, I will outlined the varied yet limited influence of CTCF, cohesin, and the chromosome loop extrusion factor NIPBL on LDB1-dependent regulatory connectivity.
The adapter molecule LMO2, which links LDB1 to transcription factors at specific genomic loci, is frequently overexpressed in T-Cell Acute Lymphoblastic Leukemia (T-ALL). I will present recent studies LDB1's role in spatially connecting enhancers to oncogenes in T-ALL.
In sum, I look forward to discussing how the LDB1 complex spatially organizes the mammalian genome in normal and cancerous cells.
About the speaker
[Biographical information about the speaker].
Meet the speaker
To meet with the speaker informally after the talks,sign up here [add link]. We especially encourage predocs and postdocs to take advantage of this opportunity.
Attachments
[Link to a file (for example a pdf of the seminar’s programme) - the file can be uploaded on the intranet]
Connection details
Zoom*: [link] (Meeting ID: [XXXXXXXXX], Password: [XXXXXXX])
Please note that the talk will yes/not be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question) or the “raise your hand” function and turn on your microphone.