PT  - JOURNAL ARTICLE
AU  - Riward Campelo Morillo
AU  - Xinran Tong
AU  - Wei Xie
AU  - Todd Lenz
AU  - Gayani Batugedara
AU  - Nusrat Tabassum
AU  - Lindsey M. Orchard
AU  - Wassim Daher
AU  - Dinshaw J. Patel
AU  - William S. Noble
AU  - Manuel Llinás
AU  - Karine G. Le Roch
AU  - Björn F.C. Kafsack
TI  - Homeodomain protein 1 is an essential regulator of gene expression during sexual differentiation of malaria parasites
AID  - 10.1101/2020.10.26.352583
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.26.352583
4099  - http://biorxiv.org/content/early/2020/10/27/2020.10.26.352583.short
4100  - http://biorxiv.org/content/early/2020/10/27/2020.10.26.352583.full
AB  - Transmission of Plasmodium falciparum and other malaria parasites requires differentiation from asexual blood stages into male and female gametocytes, a non-replicative sexual stage necessary for transmission to the mosquito vector. This particular transition relies on chromatin reorganization mechanisms that coordinate the silencing and activation of a large number of stage specific genes. However, the transcriptional and chromatin regulators that mediate the changes during sexual differentiation remain largely unknown. Here, we identify the previously uncharacterized Homeodomain Protein 1 (HDP1) as an essential regulator of this process. HDP1 binds DNA in a sequence-specific manner and is tightly associated with chromatin in early gametocytes and required for the critical expansion of the inner membrane complex. Loss of HDP1 leads to deregulation of heterochromatin-associated gene silencing, decreased telomere clustering and increased chromatin accessibility. We propose that HDP1 plays a crucial role in restructuring the parasite’s chromatin landscape during early sexual differentiation.Competing Interest StatementThe authors have declared no competing interest.