A network of epigenetic regulators guides developmental haematopoiesis in vivo.
The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo.
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Stem Cell Program and Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA [3].
Hsuan-Ting
HT
Huang
Katie L
KL
Kathrein
Abby
A
Barton
Zachary
Z
Gitlin
Yue-Hua
YH
Huang
Thomas P
TP
Ward
Oliver
O
Hofmann
Anthony
A
Dibiase
Anhua
A
Song
Svitlana
S
Tyekucheva
Winston
0000000286213271
W
Hide
Yi
Y
Zhou
Leonard I
LI
Zon
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D041905:Erythroid Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D060172:Morpholinos / Q000235:genetics; D060066:Protein Interaction Maps; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D059386:Reverse Genetics; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D002843:Chromatin; D060172:Morpholinos; D021122:Protein Subunits; D029961:Zebrafish Proteins