Hematopoietic transcription factors and differential cofactor binding regulatePRKACBisoform expression

Abstract

Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays. We identified 451 TAL1 target genes in K562 cells. Furthermore, we analysed the regulation of one of these genes, the catalytic subunit beta of protein kinase A (PRKACB), during megakaryopoiesis of K562 and primary human CD34+ stem cell/progenitor cells. We found that TAL1 together with hematopoietic transcription factors RUNX1 and GATA1 binds to the promoter of the isoform 3 of PRKACB (Cβ3). During megakaryocytic differentiation a coactivator complex on the Cβ3 promoter, which includes WDR5 and p300, is replaced with a corepressor complex. In this manner, activating chromatin modifications are removed and expression of the PRKACB-Cβ3 isoform during megakaryocytic differentiation is reduced. Our data uncover a role of the TAL1 complex in controlling differential isoform expression of PRKACB. These results reveal a novel function of TAL1, RUNX1 and GATA1 in the transcriptional control of protein kinase A activity, with implications for cellular signalling control during differentiation and disease.

K562 erythroleukemia line as a possible reticulocyte source to culture Plasmodium vivax and its surrogates

“…In this context, RUNX1 is an important transcription factor at the center of the miRNA regulatory pathways needed for erythropoiesis [43]. Closely linked to its modes of action are TAL1 and GATA1, which are also considered key transcription factors in hematopoietic differentiation [44]. In addition, the transcription factors Ets1 [45] and HES1 could be identified as suppressors for erythroid development [46].…”

Genome-Wide DNA Methylation Profiling in Early Stage I Lung Adenocarcinoma Reveals Predictive Aberrant Methylation in the Promoter Region of the Long Noncoding RNA PLUT: An Exploratory Study

“…The reporter gene assay was performed as previously described. 31 The promoter region of the long noncoding RNA (lncRNA) PLUT was amplified from genomic DNA using phusion polymerase (Thermo Scientific) and inserted in the luciferase vector pGL4.10 (Promega). Luciferase activity was measured 48 hours after transfection into HEK-293 cells and normalized to the activity of a cotransfected cytomegalovirus promoter-driven bgalactosidase vector.…”

Educação Em Saúde: Uma Proposta De Resgate Para Pacientes Cadastrados No Programa Hiperdia Em Uma Unidade De Saúde Da Família Em Cachoeira-Ba

“…Portanto, o ambiente alimentar de jovens em vulnerabilidade social pode condicionar escolhas pouco saudáveis que têm grande possibilidade de se consolidarem como padrão alimentar na idade adulta, resultando no desenvolvimento de doenças crônicas, como a obesidade e outras morbidades geralmente associadas a ela. Nessa direção, Teo et al (2014) afirmam que adolescentes em vulnerabilidade têm consumo de frutas e hortaliças inadequado, ou seja, em quantidades menores do que a recomendada, de três porções diárias. Assim, considerando que o ambiente alimentar tem influência no padrão de consumo da população, principalmente no que se refere aos adolescentes, podendo contribuir para escolhas alimentares pouco saudáveis, este trabalho teve por objetivo analisar o ambiente alimentar dos adolescentes em vulnerabilidade assistidos por um programa social em Chapecó, SC.…”