title: Ldb1 regulates carbonic anhydrase 1 during erythroid differentiation.
abstract: Carbonic anhydrase 1 (Car1), an early specific marker of the erythroid differentiation, has been used to distinguish fetal and adult erythroid cells since its production closely follows the γ- to β-globin transition, but the molecular mechanism underlying transcriptional regulation of Car1 is unclear. Here, we show that Car1 mRNA decreases significantly when erythroid differentiation is induced in MEL cells. The Ldb1 protein complex including GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced enrichment of the complex during differentiation correlates with loss of Car1 expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for recruitment of Pol II as well as the transcription regulator P-TEFb to enhance elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a regulatory complex to maintain Car1 expression in erythroid cells.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. song1030@snu.ac.kr
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Song
authors.forename: Aeri
authors.initials: A
authors.lastname: Kim
authors.forename: Ryan
authors.initials: R
authors.lastname: Dale
authors.forename: Ann
authors.initials: A
authors.lastname: Dean
mesh_terms: D000818:Animals; D024401:Carbonic Anhydrase I / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; D005914:Globins; D042925:Positive Transcriptional Elongation Factor B; C467972:Cdk9 protein, mouse; D042863:Cyclin-Dependent Kinase 9; D012321:DNA-Directed RNA Polymerases; D024401:Carbonic Anhydrase I