Faculty and Research Interests
Hristo Houbaviy, PhD
Science Center 211A
The Rockefeller University, NY, USA
PhD (Molecular Biophysics), 1999
My laboratory studies the function of miRNAs in embryonic stem cells and the early mouse embryo. Specifically, we focus on a group of homologous microRNAs (miR-290-295/miR-371-373) that are produced from a common gene, are remarkably variable and exist only in placental mammals but not in lower vertebrates (Figure 1). These miRNAs are expressed in undifferentiated ES cells where they account for at least two thirds of the total miRNA pool and are down regulated during ES cell differentiation. In the mouse, the expression of miR-290-295 is restricted to the early embryo and the germ cell precursors (Figure 2). Loss of miR-290-295 function results in developmental defects and female sterility due to impaired primordial germ cell migration. Presently, we are trying to identify the mRNA targets repressed by the mouse miR-290-295 via biochemical, genetic and bioinformatics approaches.
Figure 1. Bioinformatic definition of the eutherian miR-290-295 homologs. (A)Schematic representation of the murine miR-290-295 and human miR 371-373 loci and their canine and bovine homologs. Sequence features are given according to the legend. (B) Multiple sequence alignment of the murine (miR-290-295), human (miR-371-373), canine (predicted cf-A-C) and bovine (predicted bt-A, B) pre-miRNA hairpins. The positions of the most abundant mature miRNA clones are boxed and the two strands of the hairpin stem are underlined. (C) Multiple sequence alignment.
(click for larger version)
Figure 2. Expression pattern of miR-293 in the mouse embryo. microRNA miR-293 was detected via in situ hybridization with a digoxigenin-labeled locked nucleic acid (LNA) probe (A, C, E). The signal obtained with a probe against miR-196a, which serves as a negative control, is given in B, D, F. Sagittal frozen sections of decidua at E6.5 (A, B), E7.5 (C, D) and E8.5 (E, F) are shown with embryonic structures annotated in D.
(click for larger version)
(Updated December 2014)
- Wu S, Aksoy M, Shi J, Houbaviy HB. Evolution of the miR-290-295/miR-371-373 cluster family seed repertoire. PLoS One, 9(9): e108519, September 2014.
- Medeiros LA, Dennis LM, Gill ME, Houbaviy H, Markoulaki S, Fu D, White AC, Kirak O, Sharp PA, Page DC, Jaenisch R. Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects. Proc Natl Acad Sci, 108(34): 14163-8, August 2011.
- Houbaviy HB, Dennis L, Jaenisch R, Sharp PA. Characterization of a highly variable eutherian microRNA gene. RNA, 11(8):1245-57, August 2005.
- Houbaviy HB, Murray MF, Sharp PA. Embryonic stem cell-specific MicroRNAs. Dev Cell, 5(2): 351-8, August 2003.
- Houbaviy HB, Burley SK. Thermodynamic analysis of the interaction between YY1 and the AAV P5 promoter initiator element. Chem Biol, 8(2): 179-87, February 2001.
- Houbaviy HB, Usheva A, Shenk T, Burley SK. Cocrystal structure of YY1 bound to the adeno-associated virus P5 initiator. Proc Natl Acad Sci, 93(24): 13577-82, November 1996.
- Usheva A, Maldonado E, Goldring A, Lu C, Houbavi HB, Reinberg D, Aloni Y. Specific interaction between the nonphosphorylated form of RNA polymerase II and the TATA-binding protein. Cell, 69: 871-81, May 1992.