Cohesin regulates MHC class II genes through interactions with MHC class II insulators.
نویسندگان
چکیده
Cohesin is a multiprotein, ringed complex that is most well-known for its role in stabilizing the association of sister chromatids between S phase and M. More recently, cohesin was found to be associated with transcriptional insulators, elements that are associated with the organization of chromatin into regulatory domains. The human MHC class II (MHC-II) locus contains 10 intergenic elements, termed MHC-II insulators, which bind the transcriptional insulator protein CCCTC-binding factor. MHC-II insulators interact with each other, forming a base architecture of discrete loops and potential regulatory domains. When MHC-II genes are expressed, their proximal promoter regulatory regions reorganize to the foci established by the interacting MHC-II insulators. MHC-II insulators also bind cohesin, but the functional role of cohesin in regulating this system is not known. In this article, we show that the binding of cohesin to MHC-II insulators occurred irrespective of MHC-II expression but was required for optimal expression of the HLA-DR and HLA-DQ genes. In a DNA-dependent manner, cohesin subunits interacted with CCCTC-binding factor and the MHC-II-specific transcription factors regulatory factor X and CIITA. Intriguingly, cohesin subunits were important for DNA looping interactions between the HLA-DRA promoter region and a 5' MHC-II insulator but were not required for interactions between the MHC-II insulators themselves. This latter observation introduces cohesin as a regulator of MHC-II expression by initiating or stabilizing MHC-II promoter regulatory element interactions with the MHC-II insulator elements, events that are required for maximal MHC-II transcription.
منابع مشابه
A Case of Probable MHC Class II Deficiency with Disseminated BCGitis
Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency disease characterized by abnormality of MHC class II molecules surface expression on peripheral blood lymphocytes and monocytes. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections but the immunodeficiency is not as severe as SCID (severe combined immunodeficien...
متن کاملAnalysis of polymorphism of MHC class II BuLA DRB3 exon 2 gene in North West Iranian populations of the Water buffalo (Bubalus bubalis) through PCR-SSCP
The DRB3 gene is a highly polymorphic major histocompatibility complex (MHC) class II gene and plays an important role in variability of immune responsiveness and disease resistance. In the present study, the MHC class II DRB3 gene in water buffalo (Bubalus bubalis) populations from Northwest regions of Iran was investigated through PCR-SSCP. Genomic DNA was extracted from whole blood samples c...
متن کاملOral tolerance for delayed type hypersensitivity contribution of local and peripheral mechanisms
Oral tolerance is a physiological immune mechanism, which controls the outcome of deleterious hypersensitivity reactions to environmental antigens absorbed through the gastrointestinal tract, and maintains homeostasis. Using a mouse model of oral tolerance of delayed type hypersensitivity to contact allergens, i.e. haptens, we have examined the mechanisms involved in the induction of oral toler...
متن کاملRegulation of MHC Class II-Peptide Complex Expression by Ubiquitination
MHC class II (MHC-II) molecules are present on antigen presenting cells (APCs) and these molecules function by binding antigenic peptides and presenting these peptides to antigen-specific CD4(+) T cells. APCs continuously generate and degrade MHC-II molecules, and ubiquitination of MHC-II has recently been shown to be a key regulator of MHC-II expression in dendritic cells (DCs). In this mini-r...
متن کاملExpression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes
The small GTPase RAB4 regulates endocytic recycling, a process that contributes to Major Histocompatibility Complex (MHC)-mediated antigen presentation by specialized antigen presenting cells (APC) of the immune system. The gene encoding the RAB4B isoform of RAB4 was singled out by two complementary genome-wide screens. One of these consisted of a computer scan to identify genes containing char...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 187 8 شماره
صفحات -
تاریخ انتشار 2011