Related Experiment Video

Updated: Apr 17, 2026

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

13.4K

MCPH1 maintains long-term epigenetic silencing of ANGPT2 in chronic lymphocytic leukemia

Pradeep Kumar Kopparapu1, Caroline Miranda1, Linda Fogelstrand1

  • 1Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Sweden.

The FEBS Journal
|February 24, 2015
PubMed

Insights

Microcephalin (MCPH1), a tumor suppressor, regulates Angiopoietin 2 (ANGPT2) in chronic lymphocytic leukemia (CLL). MCPH1 silences ANGPT2 by recruiting DNA methyltransferases, impacting cancer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Deregulation of angiogenesis is a hallmark of cancers, including chronic lymphocytic leukemia (CLL).
  • Angiopoietin 2 (ANGPT2) is a key regulator of tumor angiogenesis and a prognostic marker in CLL.
  • Microcephalin (MCPH1), a tumor suppressor involved in DNA damage response, is located on the same chromosome as ANGPT2.

Purpose of the Study:

  • To investigate the functional role of MCPH1 in regulating ANGPT2 expression in CLL.
  • To explore the mechanism by which MCPH1 influences ANGPT2 in the context of CLL prognosis.

Main Methods:

  • Analysis of mRNA expression levels of MCPH1, ANGPT2, and hTERT in CLL prognostic groups.
  • Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation assays.
  • Assessment of promoter DNA methylation of ANGPT2.

Main Results:

  • MCPH1, ANGPT2, and hTERT mRNA expression levels differed significantly between IGHV-mutated and IGHV-unmutated CLL prognostic groups.
  • MCPH1 expression inversely correlated with hTERT and ANGPT2 expression.
  • Downregulation of MCPH1 led to ANGPT2 upregulation and loss of its promoter methylation.
  • MCPH1 binds to the ANGPT2 promoter and recruits DNA methyltransferases to silence ANGPT2.

Conclusions:

  • MCPH1 plays a novel role in regulating and maintaining ANGPT2 silencing in CLL.
  • MCPH1's mechanism involves the regulation of ANGPT2 promoter DNA methylation.
  • This finding provides new insights into the molecular mechanisms underlying CLL pathogenesis and prognosis.
Keywords:
ANGPT2DNA methylationMCPH1chronic lymphocytic leukemia

More Related Videos

Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients13:21

Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients

Published on: June 16, 2017

10.7K
Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

7.8K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
4.3K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.6K
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.9K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
14.1K