Functional interplay of SP family members and nuclear factor Y is essential for transcriptional activation of the human Calreticulin gene

Schardt, Julian; Keller, Manuela; Seipel, Katja; Pabst, Thomas (2015). Functional interplay of SP family members and nuclear factor Y is essential for transcriptional activation of the human Calreticulin gene. Biochimica et biophysica acta - gene regulatory mechanisms, 1849(9), pp. 1188-1197. Elsevier 10.1016/j.bbagrm.2015.07.003

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Calreticulin (CALR) is a highly conserved, multifunctional protein involved in a variety of cellular processes including the maintenance of intracellular calcium homeostasis, proper protein folding, differentiation and immunogenic cell death. More recently, a crucial role for CALR in the pathogenesis of certain hematologic malignancies was discovered: in clinical subgroups of acute myeloid leukemia, CALR overexpression mediates a block in differentiation, while somatic mutations have been found in the majority of patients with myeloproliferative neoplasms with nonmutated Janus kinase 2 gene (JAK2) or thrombopoietin receptor gene (MPL). However, the mechanisms underlying CALR promoter activation have insufficiently been investigated so far. By dissecting the core promoter region, we could identify a functional TATA-box relevant for transcriptional activation. In addition, we characterized two evolutionary highly conserved cis-regulatory modules (CRMs) within the proximal promoter each composed of one binding site for the transcription factors SP1 and SP3 as well as for the nuclear transcription factor Y (NFY) and we verified binding of these factors to their cognate sites in vitro and in vivo.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)

UniBE Contributor:

Schardt, Julian; Seipel, Katja and Pabst, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1874-9399

Publisher:

Elsevier

Language:

English

Submitter:

Marianne Zahn

Date Deposited:

17 Mar 2016 14:40

Last Modified:

29 May 2017 17:47

Publisher DOI:

10.1016/j.bbagrm.2015.07.003

PubMed ID:

26162987

Uncontrolled Keywords:

Core promoter; NFY; SP1; cis-Regulatory module

BORIS DOI:

10.7892/boris.77195

URI:

https://boris.unibe.ch/id/eprint/77195

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