Article on the subject of American region (4)
I believe the answer is:
area
'region' is the definition.
(I know that area is a type of region)
'article on the subject of american' is the wordplay.
'article' becomes 'a' (the indefinite article in English).
'on the subject of' becomes 're' (re means regarding a certain topic).
'american' becomes 'a' (common abbreviation - e.g. in organisation names).
'a'+'re'+'a'='AREA'
(Other definitions for area that I've seen before include "The measure of a surface" , "topic" , "Extent of a 2-dimensional surface" , "Space for a specific purpose, say picnic" , "Expanse of a surface" .)