TMEM8 - a non-globin gene entrapped in the globin web.
For more than 30 years it was believed that globin gene domains included only genes encoding globin chains. Here we show that in chickens, the domain of alpha-globin genes also harbor the non-globin gene TMEM8. It was relocated to the vicinity of the alpha-globin cluster due to inversion of an approximately 170-kb genomic fragment. Although in humans TMEM8 is preferentially expressed in resting T-lymphocytes, in chickens it acquired an erythroid-specific expression profile and is upregulated upon terminal differentiation of erythroblasts. This correlates with the presence of erythroid-specific regulatory elements in the body of chicken TMEM8, which interact with regulatory elements of the alpha-globin genes. Surprisingly, TMEM8 is not simply recruited to the alpha-globin gene domain active chromatin hub. An alternative chromatin hub is assembled, which includes some of the regulatory elements essential for the activation of globin gene expression. These regulatory elements should thus shuttle between two different chromatin hubs.
Philonenko
Elena S
ES
Institute of Gene Biology of the Russian Academy of Sciences, Vavilov street 34/5, 119334 Moscow, Russia.
Klochkov
Denis B
DB
Borunova
Victoria V
VV
Gavrilov
Alexey A
AA
Razin
Sergey V
SV
Iarovaia
Olga V
OV
D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D004900:Erythroblasts / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005914:Globins / Q000235:genetics*; D006801:Humans; D007438:Introns; D020014:K562 Cells; D019901:Locus Control Region; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism
D030161:Avian Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D005914:Globins; D003850:Deoxyribonuclease I