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Abstract
For an embryo to develop properly from a single cell into a complex multicellular organism with several cell types having specialized functions requires rapid morphological changes throughout the entire embryo that must be tightly regulated. Underlying the development of each cell type, is an intricate coordination of gene expression specific to that cell type which changes as the cell matures and differentiates. The chromatin state of a gene has increasingly been found to be important for proper gene expression, with open euchromatin being accessible to proteins that modulate transcription, and heterochromatin silencing transcription. The state of chromatin is controlled by several chromatin writer and eraser proteins that post-translationally modify histone tails to confer a more open or closed chromatin confirmation and recruit chromatin readers to influence target gene transcription. One such reader protein, ZMYND11, has been shown to specifically bind histone variant H3.3, which is incorporated into transcriptionally active genes. Once bound to chromatin, ZMYND11 recruits other proteins to modulate target gene expression, although the mechanism underlying ZMYND11’s ability to regulate gene expression is poorly understood. Interestingly, ZMYND11 has been found to be mutated in blood cancers and patients born with ZMYND11 haploinsufficiency experience recurrent infections. To better understand the function of zmynd11 in blood cell development, we created a mutant line of zebrafish. Our studies show that in the absence of zmynd11, primitive red blood cells over-proliferate and may have problems properly specifying cell fate. Spepcifically, RNA-seq analysis found that several genes involved in proliferation and master regulators of erythrocyte lineage specification were dysregulated, as well as the upregulation of several heat shock proteins that are primarily expressed in response to cellular stress. Our results show that zmynd11 is required for proper proliferation and lineage specification of primitive erythrocytes in zebrafish.