Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution

@article{citeulike:1181229, abstract = {Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human chromosome 7 have been suggested to play a role in the aetiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Kr\&\#252;ppel-like family of transcription factors located at chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin-immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from Dnmt3a conditional knockout mice reveals that the gene\&\#39;s expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human-lineage with a significantly increased number of non-synonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage.}, author = {Parker-Katiraee, Layla and Carson, Andrew R. and Yamada, Takahiro and Arnaud, Philippe and Feil, Robert and Abu-Amero, Sayeda N. and Moore, Gudrun and Kaneda, Masahiro and Perry, George and Stone, Anne C. and Lee, Charles and Meguro-Horike, Makiko and Sasaki, Hiroyuki and Kobayashi, Keiko and Nakabayashi, Kazuhiko and Scherer, Stephen W. }, citeulike-article-id = {1181229}, doi = {10.1371/journal.pgen.0030065.eor}, journal = {PLoS Genetics}, keywords = {adaptive, evolution, human, imprinting}, month = {March}, number = {2007}, pages = {e65.eor+}, posted-at = {2007-03-23 00:11:33}, priority = {2}, title = {Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution}, url = {http://dx.doi.org/10.1371/journal.pgen.0030065.eor}, volume = {preprint}, year = {2007} }

TY - JOUR ID - citeulike:1181229 L3 - citeulike-article-id:1181229 TI - Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution JF - PLoS Genetics VL - preprint IS - 2007 SP - e65.eor N2 - Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human chromosome 7 have been suggested to play a role in the aetiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin-immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from Dnmt3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human-lineage with a significantly increased number of non-synonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage. KW - adaptive KW - evolution KW - human KW - imprinting AU - Parker-Katiraee, Layla AU - Carson, Andrew AU - Yamada, Takahiro AU - Arnaud, Philippe AU - Feil, Robert AU - Abu-Amero, Sayeda AU - Moore, Gudrun AU - Kaneda, Masahiro AU - Perry, George AU - Stone, Anne AU - Lee, Charles AU - Meguro-Horike, Makiko AU - Sasaki, Hiroyuki AU - Kobayashi, Keiko AU - Nakabayashi, Kazuhiko AU - Scherer, Stephen PY - 2007/03/01/ UR - http://dx.doi.org/10.1371/journal.pgen.0030065.eor ER -