title: Dynamic long-range chromatin interactions control Myb proto-oncogene transcription during erythroid development.
abstract: The key haematopoietic regulator Myb is essential for coordinating proliferation and differentiation. ChIP-Sequencing and Chromosome Conformation Capture (3C)-Sequencing were used to characterize the structural and protein-binding dynamics of the Myb locus during erythroid differentiation. In proliferating cells expressing Myb, enhancers within the Myb-Hbs1l intergenic region were shown to form an active chromatin hub (ACH) containing the Myb promoter and first intron. This first intron was found to harbour the transition site from transcription initiation to elongation, which takes place around a conserved CTCF site. Upon erythroid differentiation, Myb expression is downregulated and the ACH destabilized. We propose a model for Myb activation by distal enhancers dynamically bound by KLF1 and the GATA1/TAL1/LDB1 complex, which primarily function as a transcription elongation element through chromatin looping.
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ralph
authors.initials: R
authors.lastname: Stadhouders
authors.forename: Supat
authors.initials: S
authors.lastname: Thongjuea
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andrieu-Soler
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Palstra
authors.forename: Jan Christian
authors.initials: JC
authors.lastname: Bryne
authors.forename: Anita
authors.initials: A
authors.lastname: van den Heuvel
authors.forename: Mary
authors.initials: M
authors.lastname: Stevens
authors.forename: Ernie
authors.initials: E
authors.lastname: de Boer
authors.forename: Christel
authors.initials: C
authors.lastname: Kockx
authors.forename: Antoine
authors.initials: A
authors.lastname: van der Sloot
authors.forename: Mirjam
authors.initials: M
authors.lastname: van den Hout
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb