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c-Myb Binding Sites in Haematopoietic Chromatin Landscapes.

Bengtsen M, Klepper K, Gundersen S, Cuervo I, Drabløs F, Hovig E, Sandve GK, Gabrielsen OS, Eskeland R - PLoS ONE (2015)

Bottom Line: Furthermore, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons.We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes.Our data suggest that c-Myb is a transcription factor with multifaceted target regulation depending on cell type.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.

ABSTRACT
Strict control of tissue-specific gene expression plays a pivotal role during lineage commitment. The transcription factor c-Myb has an essential role in adult haematopoiesis and functions as an oncogene when rearranged in human cancers. Here we have exploited digital genomic footprinting analysis to obtain a global picture of c-Myb occupancy in the genome of six different haematopoietic cell-types. We have biologically validated several c-Myb footprints using c-Myb knockdown data, reporter assays and DamID analysis. We show that our predicted conserved c-Myb footprints are highly dependent on the haematopoietic cell type, but that there is a group of gene targets common to all cell-types analysed. Furthermore, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons. We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes. Our data suggest that c-Myb is a transcription factor with multifaceted target regulation depending on cell type.

No MeSH data available.


Related in: MedlinePlus

c-Myb controls differentiation and cell development.(A) Gain and loss of c-Myb footprints between CD34+ cells and CD20+ and Th1 cells, respectively. To the right are the top enriched functions for genes nearby c-Myb footprints specific for either CD20+ cells or Th1 cells as compared to CD34+ cells. For the full list of enriched functions, see S9 Fig. (B) Functional analysis of c-Myb footprints in all six cell-types. The functional analysis was made with GREAT [61].
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pone.0133280.g005: c-Myb controls differentiation and cell development.(A) Gain and loss of c-Myb footprints between CD34+ cells and CD20+ and Th1 cells, respectively. To the right are the top enriched functions for genes nearby c-Myb footprints specific for either CD20+ cells or Th1 cells as compared to CD34+ cells. For the full list of enriched functions, see S9 Fig. (B) Functional analysis of c-Myb footprints in all six cell-types. The functional analysis was made with GREAT [61].

Mentions: To understand how c-Myb exerts its function through downstream gene programs, we assigned molecular functions to the identified c-Myb footprints through the use of the Gene Ontology (GO) tool GREAT [61,62] (Fig 5, S6–S9 Figs). For K562 cells the top enriched functions were identified to be in three groups: RNA catabolic processes, regulation of gene expression and cell cycle regulation (S6 Fig). This result correlates well with previous conclusions after c-Myb knockdown in the same cell type [1]. The functional analysis of the five other cell-types showed genes involved in cellular maintenance and several cell-specific functions were enriched for each cell type (S6–S9 Figs). We repeated the analysis for the same number of randomly selected DNase I footprints in all six cell-types and obtained results showing different gene functions from those predicted from the c-Myb footprint gene list.


c-Myb Binding Sites in Haematopoietic Chromatin Landscapes.

Bengtsen M, Klepper K, Gundersen S, Cuervo I, Drabløs F, Hovig E, Sandve GK, Gabrielsen OS, Eskeland R - PLoS ONE (2015)

c-Myb controls differentiation and cell development.(A) Gain and loss of c-Myb footprints between CD34+ cells and CD20+ and Th1 cells, respectively. To the right are the top enriched functions for genes nearby c-Myb footprints specific for either CD20+ cells or Th1 cells as compared to CD34+ cells. For the full list of enriched functions, see S9 Fig. (B) Functional analysis of c-Myb footprints in all six cell-types. The functional analysis was made with GREAT [61].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514710&req=5

pone.0133280.g005: c-Myb controls differentiation and cell development.(A) Gain and loss of c-Myb footprints between CD34+ cells and CD20+ and Th1 cells, respectively. To the right are the top enriched functions for genes nearby c-Myb footprints specific for either CD20+ cells or Th1 cells as compared to CD34+ cells. For the full list of enriched functions, see S9 Fig. (B) Functional analysis of c-Myb footprints in all six cell-types. The functional analysis was made with GREAT [61].
Mentions: To understand how c-Myb exerts its function through downstream gene programs, we assigned molecular functions to the identified c-Myb footprints through the use of the Gene Ontology (GO) tool GREAT [61,62] (Fig 5, S6–S9 Figs). For K562 cells the top enriched functions were identified to be in three groups: RNA catabolic processes, regulation of gene expression and cell cycle regulation (S6 Fig). This result correlates well with previous conclusions after c-Myb knockdown in the same cell type [1]. The functional analysis of the five other cell-types showed genes involved in cellular maintenance and several cell-specific functions were enriched for each cell type (S6–S9 Figs). We repeated the analysis for the same number of randomly selected DNase I footprints in all six cell-types and obtained results showing different gene functions from those predicted from the c-Myb footprint gene list.

Bottom Line: Furthermore, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons.We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes.Our data suggest that c-Myb is a transcription factor with multifaceted target regulation depending on cell type.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.

ABSTRACT
Strict control of tissue-specific gene expression plays a pivotal role during lineage commitment. The transcription factor c-Myb has an essential role in adult haematopoiesis and functions as an oncogene when rearranged in human cancers. Here we have exploited digital genomic footprinting analysis to obtain a global picture of c-Myb occupancy in the genome of six different haematopoietic cell-types. We have biologically validated several c-Myb footprints using c-Myb knockdown data, reporter assays and DamID analysis. We show that our predicted conserved c-Myb footprints are highly dependent on the haematopoietic cell type, but that there is a group of gene targets common to all cell-types analysed. Furthermore, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons. We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes. Our data suggest that c-Myb is a transcription factor with multifaceted target regulation depending on cell type.

No MeSH data available.


Related in: MedlinePlus