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2015 ; 5
(ä): 18388
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The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a
pluripotency sub-network that includes DPPA4, a regulator of embryogenesis
#MMPMID26687479
Oliviero G
; Munawar N
; Watson A
; Streubel G
; Manning G
; Bardwell V
; Bracken AP
; Cagney G
Sci Rep
2015[Dec]; 5
(ä): 18388
PMID26687479
show ga
PCGF1 encodes one of six human Polycomb RING finger homologs that are linked to
transcriptional repression and developmental gene regulation. Individual PCGF
proteins define discrete Polycomb Repressor Complex 1 (PRC1) multi-protein
complexes with diverse subunit composition whose functions are incompletely
understood. PCGF1 is a component of a variant PRC1 complex that also contains the
BCL6 co-repressor BCOR and the histone demethylase KDM2B. To further investigate
the role of PCGF1, we mapped the physical interactions of the protein under
endogenous conditions in a cell model of neuronal differentiation. Using
stringent statistical cut-offs, 83 highly enriched interacting proteins were
identified, including all previously reported members of the variant PRC1 complex
containing PCGF1, as well as proteins linked to diverse cellular pathways such as
chromatin and cell cycle regulation. Notably, a sub-network of proteins
associated with the establishment and maintenance of pluripotency (NANOG, OCT4,
PATZ1, and the developmental regulator DPPA4) were found to independently
interact with PCGF1 in a subsequent round of physical interaction mapping
experiments. Furthermore, knockdown of PCGF1 results in reduced expression of
DPPA4 and other subunits of the variant PRC1 complex at both mRNA and protein
levels. Thus, PCGF1 represents a physical and functional link between Polycomb
function and pluripotency.