Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm to regulate the divergence of hematopoietic and cardiac lineages Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape As the blood lineage emerges Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers whereas cardiac enhancers are decommissioned by removal of active epigenetic marks Our data suggest that rather than recruiting corepressors to enhancers Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors such as Gata4 and Hand1 use for gene activation Although hematopoietic Gata factors bind with Scl to both activated and repressed genes they are dispensable for cardiac repression but necessary for activating genes that enable hematopoietic stem/progenitor cell development These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated

Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence / Org, T; Duan, D; Ferrari, R; Montel-Hagen, A; Van Handel, B;  kerenyi, Ma; Sasidharan, R; Rubbi, L; Fujiwara, Y; Pellegrini, M; Orkin, Sh; Kurdistani, Sk; Mikkola, Hka. - In: EMBO JOURNAL. - ISSN 0261-4189. - 34:6(2015), pp. 759-777. [1015252/embj201490542]

Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence

Ferrari R;
2015-01-01

Abstract

Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm to regulate the divergence of hematopoietic and cardiac lineages Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape As the blood lineage emerges Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers whereas cardiac enhancers are decommissioned by removal of active epigenetic marks Our data suggest that rather than recruiting corepressors to enhancers Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors such as Gata4 and Hand1 use for gene activation Although hematopoietic Gata factors bind with Scl to both activated and repressed genes they are dispensable for cardiac repression but necessary for activating genes that enable hematopoietic stem/progenitor cell development These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated
2015
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence / Org, T; Duan, D; Ferrari, R; Montel-Hagen, A; Van Handel, B;  kerenyi, Ma; Sasidharan, R; Rubbi, L; Fujiwara, Y; Pellegrini, M; Orkin, Sh; Kurdistani, Sk; Mikkola, Hka. - In: EMBO JOURNAL. - ISSN 0261-4189. - 34:6(2015), pp. 759-777. [1015252/embj201490542]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2874927
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