Identification of a HoxA10 Activation Domain Necessary for Transcription of the Gene Encoding β3 Integrin during Myeloid Differentiation

Transcription of the ITGB3 gene, which encodes β3 integrin, increases during myeloid differentiation. αvβ3 integrin mediates adhesion to fibronectin or vitronectin and regulates various aspects of the inflammatory response in mature phagocytes. In these studies, we found that the homeodomain transcription factor HoxA10 interacted with a specific ITGB3 cis element and activated transcription of this gene during myeloid differentiation. We also found that increased fibronectin adhesion in differentiating myeloid cells was dependent upon this HoxA10-induced increase in β3 integrin expression. We determined that activation of ITGB3 transcription required a HoxA10 domain that was not identical to the “hexapeptide” that mediates interaction of Hox and Pbx proteins. This activation domain was also not identical to a previously identified HoxA10 repression domain that mediates interaction with transcriptional co-repressors. Instead, this HoxA10 activation domain had homology to “PQ” protein-protein interaction domains that have been described previously in other transcription factors. Consistent with this, we found that the HoxA10 PQ-like domain recruited the CREB-binding protein (CBP) to the ITGB3 promoter. This was associated with an increase in local histone acetylation in vivo. In immature myeloid cells, we previously determined that HoxA10 repressed transcription of the CYBB and NCF2 genes, which encode the phagocyte oxidase proteins gp91PHOX and p67PHOX, respectively. Therefore, our studies indicated that HoxA10 either activates or represses gene transcription at various points during myelopoiesis. Our studies also suggested that HoxA10 is a bifunctional protein that is involved in dynamic regulation of multiple aspects of phagocyte phenotype and function. Transcription of the ITGB3 gene, which encodes β3 integrin, increases during myeloid differentiation. αvβ3 integrin mediates adhesion to fibronectin or vitronectin and regulates various aspects of the inflammatory response in mature phagocytes. In these studies, we found that the homeodomain transcription factor HoxA10 interacted with a specific ITGB3 cis element and activated transcription of this gene during myeloid differentiation. We also found that increased fibronectin adhesion in differentiating myeloid cells was dependent upon this HoxA10-induced increase in β3 integrin expression. We determined that activation of ITGB3 transcription required a HoxA10 domain that was not identical to the “hexapeptide” that mediates interaction of Hox and Pbx proteins. This activation domain was also not identical to a previously identified HoxA10 repression domain that mediates interaction with transcriptional co-repressors. Instead, this HoxA10 activation domain had homology to “PQ” protein-protein interaction domains that have been described previously in other transcription factors. Consistent with this, we found that the HoxA10 PQ-like domain recruited the CREB-binding protein (CBP) to the ITGB3 promoter. This was associated with an increase in local histone acetylation in vivo. In immature myeloid cells, we previously determined that HoxA10 repressed transcription of the CYBB and NCF2 genes, which encode the phagocyte oxidase proteins gp91PHOX and p67PHOX, respectively. Therefore, our studies indicated that HoxA10 either activates or represses gene transcription at various points during myelopoiesis. Our studies also suggested that HoxA10 is a bifunctional protein that is involved in dynamic regulation of multiple aspects of phagocyte phenotype and function. β3 integrin, which is encoded by the ITGB3 gene, is expressed in a variety of cell types. ITGB3 transcription occurs in hematopoietic stem cells (HSC) 2The abbreviations used are: HSC, hematopoietic stem cells; IFN, interferon; shRNA, short hairpin RNA; CREB, cAMP-response element-binding protein; CBP, CREB-binding protein; GM-CSF, granulocyte-macrophage colony-stimulating factor; M-CSF, macrophage-CSF; EMSA, electrophoretic mobility shift assay; aa, amino acid; IL, interleukin. and in various blood cell lineages (1Wall C.D. Conley P.B. Armendariz-Borunda J. Sudarshan C. Wagner J.E. Raghow R. Jennings L.K. Blood Cells, Molecules, and Diseases. 1997; 23: 361-376Crossref PubMed Scopus (5) Google Scholar). In cells of the myeloid lineage, β3 integrin participates in αvβ3 heterodimers that mediate cell adhesion to fibronectin and vitronectin (2Klingemann H.G. Dedhar S. Blood. 1989; 74: 1348-1354Crossref PubMed Google Scholar, 3Hill H.R. Augustine N.H. Williams P.A. Brown E.J. Bohnsack J.F. Infect. Immun. 1993; 61: 2334-2339Crossref PubMed Google Scholar). Fibronectin is a component of the bone marrow extracellular matrix, and fibronectin binding promotes survival of HSC and differentiating myeloid progenitor cells (4Verfaille C.M. McCarthy J.B. McGlave P.B. J. Exp. Med. 1991; 174: 693-703Crossref PubMed Scopus (184) Google Scholar, 5Bhatia R. Williams A.D. Munthe H.A. Exp. Hematol. 2002; 30: 324-332Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). Expression of β3 integrin increases during differentiation of neutrophils and monocytes (1Wall C.D. Conley P.B. Armendariz-Borunda J. Sudarshan C. Wagner J.E. Raghow R. Jennings L.K. Blood Cells, Molecules, and Diseases. 1997; 23: 361-376Crossref PubMed Scopus (5) Google Scholar). In mature αvβ3 mediates of to of the inflammatory response J. C. PubMed Scopus Google Scholar, C. P.A. J. Google Scholar). In αvβ3 a during the and is also involved in activation of the oxidase Blood. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). In to in the binding activates and involved in of cell survival in cells Blood. PubMed Scopus Google Scholar). that the that αvβ3 to cell and regulation of ITGB3 transcription during or in mature myeloid cells not been the studies of the ITGB3 in cells 2002; PubMed Scopus Google Scholar). studies identified a of the ITGB3 that in with the homeodomain transcription factor In these studies, HoxA10 activated an with this of the ITGB3 in with a cell 2002; PubMed Scopus Google Scholar). HoxA10 is expressed in differentiating myeloid cells, the of our studies was that HoxA10 regulates ITGB3 transcription during myelopoiesis. in in and gene transcription occurs to with the expressed in and the in 1989; PubMed Scopus Google Scholar). also expressed during with the expressed in and in hematopoietic cells C. S. PubMed Scopus Google Scholar). Consistent with this, expressed in myeloid of various Hox proteins is associated with myeloid that regulation of the proteins is PubMed Scopus Google Scholar). our studies indicated that proteins involved in transcription of involved in R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). Therefore, the of these studies was that dynamic regulation of ITGB3 transcription by HoxA10 to phagocyte and survival during myelopoiesis. In our studies, we found that HoxA10 regulates transcription of the the phagocyte oxidase proteins gp91PHOX and CYBB and NCF2 genes, R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). expressed in myeloid cells the of differentiation and cell C. J. S. PubMed Scopus Google Scholar, R. PubMed Scopus Google Scholar). We determined that HoxA10 represses CYBB and NCF2 transcription in myeloid In these cells, HoxA10 to CYBB and NCF2 cis a with the homeodomain protein R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). Hox and Pbx proteins and transcriptional regulation by heterodimers is by Pbx interaction with transcriptional or PubMed Scopus Google Scholar). we found that of CYBB and NCF2 transcription was and involved interaction of HoxA10 with the histone S. C. J. PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). This interaction required a HoxA10 not in other proteins J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). differentiation HoxA10 binding to the CYBB and NCF2 repression R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). gp91PHOX and the phagocyte oxidase this in differentiation of in mature phagocytes. HoxA10 also regulates ITGB3 transcription in a differentiation this that HoxA10 is an of phagocyte function. that activated by HoxA10 in myeloid cells have been not been previously studies, HoxA10 to ITGB3 transcription during myelopoiesis. Therefore, the of these studies was to HoxA10 increases β3 integrin and in differentiating myeloid of these studies was to the of regulation of β3 integrin of these studies was to HoxA10 activation of ITGB3 transcription a Pbx transcriptional activation is not ITGB3 transcription used a to a HoxA10 activation Therefore, these studies phagocyte and also of HoxA10 transcription factor described previously R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google in the H.R. R. J. 1989; PubMed Scopus Google at the of with the of the to the ITGB3 2002; PubMed Scopus Google Scholar, Blood. PubMed Google Scholar). and HoxA10 was C. of J. C. 1991; PubMed Scopus Google Scholar). This the in hematopoietic cells, a protein J. C. 1991; PubMed Scopus Google Scholar). HoxA10 was the in cells PubMed Google Scholar). HoxA10 was also the in cells a protein with the domain of the transcription factor described previously R. J. Full Text Full Text PDF PubMed Scopus Google Scholar). HoxA10 by that the HoxA10 and an that HoxA10 amino and the a protein with the domain of the transcription HoxA10 also amino and the in HoxA10 with of the interaction domain by by a previously described J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). HoxA10 was to amino to and amino to This was a in by to that had been to to β3 integrin or HoxA10 the by β3 shRNA, shRNA, or with the of the the by the of the at the to of the ITGB3 or the to of the CYBB In these the HoxA10 is in the Pbx is in and the In an the was also cell J. PubMed Google was at the of and described R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). cells with of or indicated marrow was or and myeloid progenitor cells in and stem cell factor cells in to a by the and proteins by the of 1993; Scopus Google with described previously R. J. Full Text Full Text PDF PubMed Scopus Google Scholar). and described R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). to HoxA10 with other Hox was and to and with other or other Pbx with at of and by described R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). cells with of or of and of In cells also with a to the R. J. PubMed Google Scholar). at with and of cell and described R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). In other cells with of and of a to HoxA10 or various proteins with the domain of the transcription In cells also with a to the of protein used in these was determined in studies in which the various HoxA10 to the of repression and repression was with of with our with this J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). with a to HoxA10 or in or described previously R. J. Full Text Full Text PDF PubMed Scopus Google Scholar). In cells with to β3 integrin or cell proteins cells or various by and to with to various proteins. to β3 integrin was to and was at and other proteins with of or with domain or described proteins by and with to or the domain This was and was cells the to was by to the of the and was with the and was to the to and to in various In other was that cells with an to the CREB-binding protein or was with the cis element in the ITGB3 promoter. was a to in the various at with cells with or and to fibronectin at In cells with of to integrin, β3 integrin, or to with and cells in at cells at with and in and at was determined a of adhesion J. Full Text Full Text PDF PubMed Scopus Google Scholar). In other studies, bone monocytes fibronectin these studies, cells to and adhesion was determined by and of the and β3 Expression and β3 Fibronectin during of of these studies was to HoxA10 regulates ITGB3 β3 integrin and phagocyte adhesion in differentiating myeloid Therefore, we to the cell was a these cells a myeloid that differentiation upon with various J. PubMed Google Scholar). differentiation of cells in of of mature and cell In studies, we determined that HoxA10 protein is expressed in cells and that is not by differentiation R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). Therefore, this cell a to these of myeloid differentiation. We determined the of differentiation β3 integrin expression. In of we found that of β3 integrin protein increased during the of differentiation this increase in β3 integrin protein with an increase in we determined the of β3 integrin by these studies, of the oxidase gp91PHOX and and was to and S. Consistent with the protein we found that increased β3 integrin in cells studies indicated a increase in β3 integrin, and during differentiation these studies not a to increased β3 integrin during myeloid differentiation. Therefore, we the of β3 integrin in fibronectin adhesion of differentiating We to this interaction fibronectin is an extracellular component involved in survival of hematopoietic cells R. Williams A.D. Munthe H.A. Exp. Hematol. 2002; 30: 324-332Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). with fibronectin is also in phagocyte Blood. PubMed Scopus Google Scholar). In these studies, we found that of differentiation increased cell adhesion to fibronectin αvβ3 and heterodimers mediate myeloid cell adhesion to we determined the of to β3 integrin We found that with adhesion of cells to fibronectin not fibronectin adhesion of cells In with an to β3 integrin not adhesion of cells to fibronectin differentiation not fibronectin adhesion of cells with β3 integrin the specific of β3 integrin fibronectin with a to a β3 or We found that differentiation increased fibronectin adhesion of with cells of a β3 fibronectin adhesion of β3 to not adhesion to fibronectin of cells, with the studies HoxA10 Expression β3 Expression and Fibronectin of we determined the of HoxA10 β3 integrin and fibronectin adhesion of these studies, cells with a to HoxA10 or and by of β3 integrin and HoxA10 a We found increased β3 integrin in in with with and differentiation HoxA10 in by differentiation of the with our R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). We also activation of a of β3 integrin that mediates cell survival Blood. PubMed Scopus Google Scholar). these studies, the with to and We found increased in with increased β3 integrin in these cells In is in or with or We also the to the of HoxA10 protein β3 integrin and fibronectin these studies, with a to a or these of β3 integrin and with and differentiation We found that of HoxA10 β3 integrin in differentiating We also fibronectin adhesion of with either HoxA10 or HoxA10 to the of β3 integrin in these We found that HoxA10 increased adhesion to fibronectin in and We also found that of a fibronectin adhesion in in with with studies suggested that HoxA10 β3 integrin and fibronectin adhesion in differentiating myeloid HoxA10 β3 Expression and β3 in also the of HoxA10 β3 integrin and fibronectin adhesion of bone these studies, myeloid progenitor cells the bone marrow of or cells in GM-CSF, and stem cell factor by differentiation to monocytes with S. C. J. PubMed Scopus Google Scholar). We determined the of HoxA10 β3 integrin by of proteins. We found increased β3 integrin in monocytes in with HoxA10 monocytes with the studies with HoxA10 in We also these cells fibronectin In these studies, we found that monocytes fibronectin adhesion in with monocytes studies suggested a HoxA10 in β3 integrin and cell adhesion in differentiating myeloid of β3 increased fibronectin adhesion of cells was dependent β3 integrin, with a to HoxA10 or and a to β3 or proteins by to of β3 integrin by β3 in fibronectin adhesion with and differentiation. We found that HoxA10 increased fibronectin adhesion of cells with a to shRNA, with and to the in the In HoxA10 not increase fibronectin adhesion in cells with the β3 of β3 fibronectin adhesion of HoxA10 suggested that β3 integrin was HoxA10-induced fibronectin HoxA10 a in the ITGB3 the of HoxA10 the of the ITGB3 promoter. studies in interaction of HoxA10 with a in the ITGB3 by proteins cells 2002; PubMed Scopus Google Scholar). this a cis element in myeloid cells, we an with multiple of the cis element to a and This or was cells with a to HoxA10 or with We also the and cells with these and a to a or with or of differentiation. We found that the was that this a cis element in myeloid cells We also found that this cis element was in in This was with of the cis element in ITGB3 transcription during myeloid differentiation. Therefore, we the of HoxA10 in this We found that of the ITGB3 cis element was in with and with the of HoxA10 β3 integrin protein and In of HoxA10 not with or we found that of a not of the ITGB3 cis element in in with with In of increase in element of not have this studies with the of also with the that HoxA10 ITGB3 transcription during differentiation of myeloid the ITGB3 in a this element was to binding of we HoxA10 with a Pbx protein to this cis In our studies of the CYBB and NCF2 genes, we found that HoxA10 interacted with cis in these in and in in with HoxA10 binding to these CYBB and NCF2 cis in the suggested that HoxA10 to the ITGB3 cis element in cells and activated transcription during differentiation. This suggested the that differentiation increased HoxA10 binding to the ITGB3 cis the of the HoxA10 binding to the CYBB and NCF2 Therefore, we to the of differentiation HoxA10 interaction with the ITGB3 cis these studies, proteins cells, with or of and used in binding with a the ITGB3 cis element to a also with a the CYBB cis element to In these studies, we found that of cells increased binding of a mobility protein to the ITGB3 cis element In studies, we determined that this specific protein binding to the in the with 2002; PubMed Scopus Google Scholar). Consistent with our binding of a mobility protein of mobility to the CYBB We have previously that this HoxA10 and Therefore, we to the mobility protein which to the ITGB3 cis HoxA10 a Pbx these studies, proteins cells with to or and used in with the ITGB3 We found that binding of the protein to this we found that to not also this suggested that the ITGB3 cis element was activated by a In these studies, we found that HoxA10 to the ITGB3 cis element in in suggested the that HoxA10 activated the ITGB3 in differentiating myeloid Pbx to the HoxA10 previously described genes, the Pbx protein recruited transcriptional or proteins to binding cis PubMed Scopus Google Scholar). Pbx protein was of transcription of Therefore, we HoxA10 activation of the ITGB3 cis element required interaction with a Pbx this, we used a previously described of HoxA10 with in the Pbx binding “hexapeptide” to C. PubMed Scopus Google Scholar). of these was previously to interaction of HoxA10 with Pbx proteins not binding S. C. J. PubMed Scopus Google Scholar, J. J. Full Text Full Text PDF PubMed Scopus Google Scholar, C. PubMed Scopus Google Scholar). We cells with the multiple of the ITGB3 cis element or and a to gene was determined and and we with with HoxA10 or We found that activation of the ITGB3 cis element was not in with with or differentiation In of HoxA10 of Consistent with and HoxA10 expressed in J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). suggested that the Pbx interaction domain was not identical to the HoxA10 activation Therefore, we of the domain involved in HoxA10 activation of ITGB3 transcription during myeloid differentiation. HoxA10 Transcription a to the HoxA10 activation the we expressed various HoxA10 proteins with the domain of the transcription factor to proteins by cells with a to the protein and a multiple of a to a promoter. to this was that HoxA10 in the In the of we the of HoxA10 to transcription the cis element in the ITGB3 gene the to this was that of the activation domain in the of a We the of protein a of HoxA10 proteins and Consistent with our of repression of this in in with J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). In we found that of either the protein or the protein was associated with activation of this in the protein not this in with these we was a activation domain HoxA10 amino and to this HoxA10 amino and of We found that in either or was not with or In the in was in with of these other studies suggested that the HoxA10 activation domain is amino and these we a of HoxA10 to activation of the ITGB3 cis described to the HoxA10 an and the homeodomain cells with the ITGB3 cis or or and a to or gene with and differentiation. We found that activation of the ITGB3 cis element was not in HoxA10 with and In HoxA10 and HoxA10 repressed the ITGB3 cis in with in this repression was by differentiation. the ITGB3 cis in with HoxA10 or HoxA10 was not in of these proteins with or differentiation. studies suggested that the HoxA10 activation domain was not identical to the Pbx interaction domain amino and Therefore, we in this to homology with domains in other proteins. this, we a the of of We found that this HoxA10 had homology to “PQ” domains in other transcription the protein R. J.B. PubMed Scopus Google and protein C.M. J. PubMed Scopus Google proteins gene transcription interaction with transcriptional Therefore, we HoxA10 recruited transcriptional a transcriptional Expression HoxA10 of the ITGB3 homology of the HoxA10 activation domain with the domain in the we that this domain transcriptional to the ITGB3 promoter. is a that with the transcriptional the CREB-binding protein and R. PubMed Scopus Google Scholar). with specific domains in these and interaction with transcription gene Therefore, we the of the HoxA10 activation these studies, cells with a to or a to or and a with multiple of a cis element to a promoter. We found that activation of the by in was not in with also increased repression of in this suggested that of in cells with interaction of a transcriptional and the HoxA10 PQ-like We also in the of HoxA10 activation of the ITGB3 cis these studies, cells with the with multiple of the ITGB3 cis element or a to HoxA10 or and a to or was determined with and differentiation of the In these studies, we found that HoxA10 activation of the ITGB3 cis element in and in these was not with In HoxA10 not the with or with or HoxA10 PQ-like to the ITGB3 of our studies suggested that HoxA10 activation of the ITGB3 cis element required interaction with a transcriptional interaction of transcriptional proteins with transcription factor these not Therefore, we cells with and differentiation. these studies, proteins to in and cell with an to HoxA10 or the transcriptional CBP, or by with the cis element in the ITGB3 an to to in the In these studies, we found that in HoxA10 binding to this cis element increased upon differentiation of cells We also found that differentiation increased in binding to the ITGB3 cis element In was of ITGB3 cis element in with to or in with histone to the ITGB3 cis element by HoxA10 to increase acetylation of and Therefore, we used to binding of histone to the ITGB3 cis element during differentiation. This was histone is of the histone of In these studies, we found that differentiation increased of studies suggested that HoxA10 recruited to the ITGB3 cis and this in transcriptional Therefore, we to interacted with the HoxA10 PQ-like activation these studies, cells with a to or proteins these with an to the or an proteins by and with to and the domain an Consistent with our we found that with the domain We also found that this was in with proteins the with the that and and protein was in by of the In these studies, we found that HoxA10 was required increased ITGB3 transcription and β3 integrin during myeloid differentiation. We also found that this increase in β3 integrin was to the increase in fibronectin adhesion in differentiating myeloid HoxA10 to an ITGB3 cis element a with we found that interaction with was HoxA10 activation of this cis Consistent with this, we found that the HoxA10 activation domain was not identical to the was a not in other proteins. This domain was to domains that mediate protein-protein in other transcriptional proteins. In studies, we found that the HoxA10 PQ-like domain recruited to the ITGB3 in and in vivo. Therefore, these studies identified ITGB3 a gene activated by HoxA10 in differentiating myeloid cells, determined that HoxA10 fibronectin adhesion of differentiating myeloid cells, identified a HoxA10 activation and determined that this domain recruited a transcriptional protein to a gene promoter. to in and in Hematol. PubMed Scopus Google Scholar). this, have been identified these homeodomain proteins. of Hox is of Hox proteins either or transcription of various genes, upon Consistent with this, activation and repression have been described studies identified a in the ITGB3 that was activated by HoxA10 in cells 2002; PubMed Scopus Google Scholar). In we found that the CYBB and NCF2 repressed by HoxA10 in myeloid cells R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). of β3 integrin increases during we ITGB3 transcription a transcriptional activation by HoxA10 during myeloid differentiation. the of these studies, we determined that HoxA10 activated ITGB3 transcription during myelopoiesis. Therefore, these studies identified a gene that is activated by HoxA10 and is involved in the of mature phagocytes. In these studies, we found that fibronectin adhesion of cells differentiation is dependent HoxA10-induced β3 integrin expression. We also found that HoxA10 increased activation in differentiating myeloid is associated with of cell survival Blood. PubMed Scopus Google these suggested a by which HoxA10 of differentiating myeloid This is of HoxA10 been associated with in myeloid and a in the various of β3 integrin in mature that β3 integrin cell adhesion integrin is by in integrin in of the J. Full Text Full Text PDF PubMed Scopus Google Scholar, J. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). of β3 integrin occurs PubMed Scopus Google Scholar). S. and Our studies identified an of myeloid differentiation β3 integrin increased ITGB3 suggested that β3 integrin in differentiating myeloid cells or during the inflammatory we found that differentiation of cells increased β3 fibronectin this not In of cells with increased fibronectin adhesion by integrin J. Full Text Full Text PDF PubMed Scopus Google Scholar). of integrin regulation and is and gene of of integrin and in differentiating myeloid cells is not of phagocyte function. In studies, we determined that HoxA10 the ITGB3 a with the homeodomain protein in studies, we found that interaction with was not HoxA10 activation of the ITGB3 cis heterodimers have been to or the of the Pbx to transcriptional or proteins PubMed Scopus Google Scholar). In the Hox is to the specific binding the In the studies, we identified a HoxA10 activation domain that recruited a transcriptional protein to the ITGB3 in a increase the of HoxA10 to the ITGB3 cis this was not in our is that increased HoxA10 binding of interaction with at HoxA10 not in cells In studies, we determined that the CYBB and NCF2 HoxA10 R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). In to the studies, HoxA10 repressed these in myeloid In studies, we identified a HoxA10 repression domain that with J. J. Full Text Full Text PDF PubMed Scopus Google Scholar). This domain was not identical to the activation domain identified in the studies, was not in other proteins the homeodomain and the of the proteins This that the that various in gene regulation to at We found this to the CYBB gene, which is activated in differentiating myeloid cells by interaction of with the cis element that is repressed by HoxA10 in cells J. Full Text Full Text PDF PubMed Scopus Google Scholar). In the studies, interaction of HoxA10 with the cis element in the ITGB3 gene increased during myeloid differentiation. In interaction of HoxA10 with the cis in the CYBB and NCF2 during R. J. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. J. PubMed Scopus Google Scholar). HoxA10 binding to the CYBB and NCF2 cis was to of in the homeodomain in response to differentiating J. R. J. 2002; Full Text Full Text PDF Scopus Google Scholar). increased HoxA10 interaction with the ITGB3 cis element in response to differentiation is not is a of in the involved in of the HoxA10 activation domain the HoxA10 repression domain at various of differentiation or various is that of these domains is by HoxA10 in response to the of proteins the HoxA10 activation or repression domain is at a differentiation is that various binding HoxA10 of either the activation or repression of the CYBB and NCF2 ITGB3 cis not an in differentiation interaction of HoxA10 with these or function. cis element have homology to previously described binding S. C. PubMed Scopus Google Scholar). of HoxA10 this the of proteins to and the and regulation of these proteins is In these studies, we identified a HoxA10 gene that is activated during myeloid differentiation. We this gene a to the HoxA10 activation domain and the by which this domain studies of proteins the of of these proteins in myeloid