PMID- 33536327
OWN - NLM
STAT- MEDLINE
DCOM- 20210819
LR  - 20240330
IS  - 2379-5042 (Electronic)
IS  - 2379-5042 (Linking)
VI  - 6
IP  - 1
DP  - 2021 Feb 3
TI  - Investigation of Heterochromatin Protein 1 Function in the Malaria Parasite 
      Plasmodium falciparum Using a Conditional Domain Deletion and Swapping Approach.
LID - 10.1128/mSphere.01220-20 [doi]
LID - e01220-20
AB  - The human malaria parasite Plasmodium falciparum encodes a single ortholog of 
      heterochromatin protein 1 (PfHP1) that plays a crucial role in the epigenetic 
      regulation of various survival-related processes. PfHP1 is essential for parasite 
      proliferation and the heritable silencing of genes linked to antigenic variation, 
      host cell invasion, and sexual conversion. Here, we employed CRISPR/Cas9-mediated 
      genome editing combined with the DiCre/loxP system to investigate how the PfHP1 
      chromodomain (CD), hinge domain, and chromoshadow domain (CSD) contribute to 
      overall PfHP1 function. We show that the 76 C-terminal residues are responsible 
      for targeting PfHP1 to the nucleus. Furthermore, we reveal that each of the three 
      functional domains of PfHP1 are required for heterochromatin formation, gene 
      silencing, and mitotic parasite proliferation. Finally, we discovered that the 
      hinge domain and CSD of HP1 are functionally conserved between P. falciparum and 
      P. berghei, a related malaria parasite infecting rodents. In summary, our study 
      provides new insights into PfHP1 function and offers a tool for further studies 
      on epigenetic regulation and life cycle decision in malaria parasites.IMPORTANCE 
      Malaria is caused by unicellular Plasmodium species parasites that repeatedly 
      invade and replicate inside red blood cells. Some blood-stage parasites exit the 
      cell cycle and differentiate into gametocytes that are essential for malaria 
      transmission via the mosquito vector. Epigenetic control mechanisms allow the 
      parasites to alter the expression of surface antigens and to balance the switch 
      between parasite multiplication and gametocyte production. These processes are 
      crucial to establish chronic infection and optimize parasite transmission. Here, 
      we performed a mutational analysis of heterochromatin protein 1 (HP1) in P. 
      falciparum We demonstrate that all three domains of this protein are 
      indispensable for the proper function of HP1 in parasite multiplication, 
      heterochromatin formation, and gene silencing. Moreover, expression of chimeric 
      proteins revealed the functional conservation of HP1 proteins between different 
      Plasmodium species. These results provide new insight into the function and 
      evolution of HP1 as an essential epigenetic regulator of parasite survival.
CI  - Copyright (c) 2021 Bui et al.
FAU - Bui, Hai T N
AU  - Bui HTN
AD  - Department of Medical Parasitology and Infection Biology, Swiss Tropical and 
      Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Passecker, Armin
AU  - Passecker A
AD  - Department of Medical Parasitology and Infection Biology, Swiss Tropical and 
      Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Brancucci, Nicolas M B
AU  - Brancucci NMB
AD  - Department of Medical Parasitology and Infection Biology, Swiss Tropical and 
      Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Voss, Till S
AU  - Voss TS
AUID- ORCID: 0000-0002-1464-4988
AD  - Department of Medical Parasitology and Infection Biology, Swiss Tropical and 
      Public Health Institute, Basel, Switzerland till.voss@swisstph.ch.
AD  - University of Basel, Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210203
PL  - United States
TA  - mSphere
JT  - mSphere
JID - 101674533
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Protozoan Proteins)
RN  - 107283-02-3 (Chromobox Protein Homolog 5)
SB  - IM
MH  - Antigenic Variation
MH  - CRISPR-Cas Systems
MH  - Cell Line
MH  - Chromobox Protein Homolog 5
MH  - Chromosomal Proteins, Non-Histone/*genetics/*metabolism
MH  - Erythrocytes/parasitology
MH  - Gene Expression Regulation
MH  - *Gene Silencing
MH  - Humans
MH  - Malaria, Falciparum/parasitology
MH  - Plasmodium falciparum/*genetics/metabolism
MH  - Protozoan Proteins/*genetics/metabolism
PMC - PMC7860992
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - DiCre
OT  - HP1
OT  - Plasmodium falciparum
OT  - epigenetics
OT  - heterochromatin
OT  - malaria
EDAT- 2021/02/05 06:00
MHDA- 2021/08/20 06:00
PMCR- 2021/02/03
CRDT- 2021/02/04 05:41
PHST- 2021/02/04 05:41 [entrez]
PHST- 2021/02/05 06:00 [pubmed]
PHST- 2021/08/20 06:00 [medline]
PHST- 2021/02/03 00:00 [pmc-release]
AID - 6/1/e01220-20 [pii]
AID - mSphere01220-20 [pii]
AID - 10.1128/mSphere.01220-20 [doi]
PST - epublish
SO  - mSphere. 2021 Feb 3;6(1):e01220-20. doi: 10.1128/mSphere.01220-20.