Characterization and evolutionary origin of novel C < sub > 2 < /sub > H < sub > 2 < /sub > zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans.

Characterization and evolutionary origin of novel C₂H₂ zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans.
Haematologica. 2020 Oct 05;Online ahead of print:
Authors: Ferguson DCJ, Mokim JH, Meinders M, Moody ERR, Williams TA, Cooke S, Trakarnsanga K, Daniels DE, Ferrer-Vicens I, Shoemark D, Tipgomut C, Macinnes KA, Wilson MC, Singleton BK, Frayne J
Abstract
Human ZNF648 is a novel poly C-terminal C2H2 zinc finger protein identified amongst the most dysregulated proteins in erythroid cells differentiated from iPSC. Its nuclear localisation and structure indicate it is likely a DNA-binding protein. Using a combination of ZNF648 overexpression in an iPSC line and primary adult erythroid cells, ZNF648 knockdown in primary adult erythroid cells and megakaryocytes, comparative proteomics and transcriptomics we show that ZNF648 is required for both erythroid and megakaryocyte differentiation. Orthologues of ZNF648 were detected across Mammals, Reptilia, Actinopterygii, in some Aves, Amphibia and Coelacanthiformes suggesting the gene originated in the common ancestor of Osteichthyes (Euteleostomi or bony fish). Conservation of the C-terminal zinc finger domain is higher, with some variation in zinc finger number but a core of at least six zinc fingers conserved across all groups, with the N-terminus recognisably similar within but not between majo...

Source: Haematologica - October 5, 2020 Category: Hematology Authors: Ferguson DCJ, Mokim JH, Meinders M, Moody ERR, Williams TA, Cooke S, Trakarnsanga K, Daniels DE, Ferrer-Vicens I, Shoemark D, Tipgomut C, Macinnes KA, Wilson MC, Singleton BK, Frayne J Tags: Haematologica Source Type: research