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PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein.

Abstract：

:The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS1, but not its sumoylation, is required for Msx1 to function as an inhibitor of myoblast differentiation through repression of myogenic regulatory genes, such as MyoD. We find that PIAS1 enables Msx1 to bind selectively to a key regulatory element in MyoD, the CER, in myoblast cells and to distinguish the CER from other nonregulatory TAAT-containing sequences. We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells. Furthermore, we demonstrate that myogenic regulatory genes that are repressed by Msx1, namely MyoD and Myf5, are located at the nuclear periphery in myoblast cells. We propose that a key regulatory event for DNA-binding specificity by homeoproteins in vivo is their appropriate targeting to subnuclear compartments where their target genes are located, which can be achieved by cofactors such as PIAS1.

journal_name

Genes Dev

journal_title

Genes & development

authors

Lee H,Quinn JC,Prasanth KV,Swiss VA,Economides KD,Camacho MM,Spector DL,Abate-Shen C

doi

10.1101/gad.1392006

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

784-94

issue

7

eissn

0890-9369

issn

1549-5477

pii

20/7/784

journal_volume

20

pub_type

杂志文章

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