Abstract：
:Cardiac stem/progenitor cells hold great potential for regenerative therapies; however, the mechanisms regulating their expansion and differentiation remain insufficiently defined. Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage differentiation and heart development. We demonstrate that Ldb1 binds to the key regulator of cardiac progenitors, Isl1, and protects it from degradation. Furthermore, the Isl1/Ldb1 complex promotes long-range enhancer-promoter interactions at the loci of the core cardiac transcription factors Mef2c and Hand2. Chromosome conformation capture followed by sequencing identified specific Ldb1-mediated interactions of the Isl1/Ldb1 responsive Mef2c anterior heart field enhancer with genes that play key roles in cardiac progenitor cell function and cardiovascular development. Importantly, the expression of these genes was downregulated upon Ldb1 depletion and Isl1/Ldb1 haplodeficiency. In conclusion, the Isl1/Ldb1 complex orchestrates a network for heart-specific transcriptional regulation and coordination in three-dimensional space during cardiogenesis.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Caputo L,Witzel HR,Kolovos P,Cheedipudi S,Looso M,Mylona A,van IJcken WF,Laugwitz KL,Evans SM,Braun T,Soler E,Grosveld F,Dobreva Gdoi
10.1016/j.stem.2015.08.007subject
Has Abstractpub_date
2015-09-03 00:00:00pages
287-99issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(15)00362-8journal_volume
17pub_type
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