RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements.

Abstract:

:The CD11a/CD18 (leukocyte function-associated antigen 1 [LFA-1]) integrin mediates critical leukocyte adhesive interactions during immune and inflammatory responses. The CD11a promoter directs CD11a/CD18 integrin expression, and its activity in lymphoid cells depends on a functional RUNX1/AML-1-binding site (AML-110) within the MS7 sequence. We now report that MS7 contains a C/EBP-binding site (C/EBP-100), which overlaps with AML-110 and is bound by C/EBP factors in myeloid cells. C/EBP and RUNX/AML factors compete for binding to their respective cognate elements and bind to the CD11a promoter MS7 sequence in a cell lineage- and differentiation-dependent manner. In myeloid cells MS7 is primarily recognized by C/EBP factors in proliferating cells whereas RUNX/AML factors (especially RUNX3/AML-2) bind to MS7 in differentiated cells. RUNX3/AML-2 binding to the CD11a promoter correlates with increased RUNX3/AML-2 protein levels and enhanced CD11a/CD18 cell surface expression. The relevance of the AML-110 element is underscored by the ability of AML-1/ETO to inhibit CD11a promoter activity, thus explaining the low CD11a/CD18 expression in t(8;21)-containing myeloid leukemia cells. Therefore, the expression of the CD11a/CD18 integrin in myeloid cells is determined through the differential occupancy of the CD11a proximal promoter by transcription factors implicated in the pathogenesis of myeloid leukemia.

journal_name

Blood

journal_title

Blood

authors

Puig-Kröger A,Sanchez-Elsner T,Ruiz N,Andreu EJ,Prosper F,Jensen UB,Gil J,Erickson P,Drabkin H,Groner Y,Corbi AL

doi

10.1182/blood-2003-02-0618

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

3252-61

issue

9

eissn

0006-4971

issn

1528-0020

pii

2003-02-0618

journal_volume

102

pub_type

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