University of Wisconsin–Madison
Loading Events

« All Events

  • This event has passed.

Charu Mehta, Research Assistant, Cell and Regenerative Biology (Bresnick lab)

April 17 @ 12:00 pm - 1:00 pm

Topic: Integrating Enhancer Mechanisms to establish a hierarchical blood development program

Abstract: Hematopoietic development requires the transcription factor GATA-2, and GATA-2 mutations cause diverse pathologies, including leukemia. GATA-2-regulated enhancers +9.5 and -77 differentially control Gata2 expression in hematopoietic stem/progenitor cells and are essential for hematopoiesis and embryonic development. Targeted deletion of an intronic Gata2 enhancer 9.5 kb downstream of the transcription start site (+9.5) abrogates HSC genesis in the aorta-gonad-mesonephros region. By contrast, the -77 kb enhancer (-77) activates transcription in myeloid progenitors, and its deletion impairs progenitor differentiation. Since +9.5-/- embryos are HSC deficient, it was unclear whether the +9.5 functions in progenitors or if GATA-2 expression in progenitors solely requires -77. We further dissected the mechanisms using -77;+9.5 compound heterozygous (CH) mice. The embryonic lethal CH mutation depleted megakaryocyte-erythrocyte progenitors (MEPs), differing from -77 +/- and +9.5 +/- mutants. While the +9.5 suffices for HSC generation, the -77 and +9.5 must reside on one allele to induce MEPs.

The -77 enhancer generated burst-forming unit-erythroid through the induction of GATA-1 and other GATA-2 targets. Ongoing studies are integrating GATA-2-regulated targets into signaling circuits that might constitute new regulators of erythroid cell maturation/function. Thus, loss of the -77 enhancer creates multi-faceted defects in erythroid precursors, involving deficiencies of constituents of signaling and transcriptional circuitry required to enable and drive erythroid maturation.

Details

Date:
April 17
Time:
12:00 pm - 1:00 pm
Event Category:

Venue

UW Biotechnology Center Auditorium
425 Henry Mall
Madison , WI 53705 United States
+ Google Map